Digital Commons Network^™

Gene Replacement-Alzheimer's Disease (Gr-Ad): Modeling The Genetics Of Human Dementias In Mice., Kellie Benzow, Kul Karanjeet, Adrian L Oblak, Gregory W. Carter, Michael Sasner, Michael D Koob

Faculty Research 2024

INTRODUCTION: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible.

METHODS: To do this, we are generating mouse lines in which the genes of …

A Multi-Ancestry Genetic Study Of Pain Intensity In 598,339 Veterans., Sylvanus Toikumo, Rachel Vickers-Smith, Zeal Jinwala, Heng Xu, Divya Saini, Emily E Hartwell, Mirko Pavicic, Kyle A Sullivan, Ke Xu, Daniel A Jacobson, Joel Gelernter, Christopher T Rentsch, Million Veteran Program, Eli Stahl, Martin Cheatle, Hang Zhou, Stephen G Waxman, Amy C Justice, Rachel L Kember, Henry R Kranzler

Epidemiology and Environmental Health Faculty Publications

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, …

Robust Capital Cost Optimization Of Generation And Multitimescale Storage Requirements For A 100% Renewable Australian Electricity Grid, Raheel A Shaikh, David J Vowles, Alex Dinovitser, Andrew Allison, Derek Abbott

Faculty, Staff and Student Publications

Transitioning from a fossil-fuel-dependent economy to one based on renewable energy requires significant investment and technological advancement. While wind and solar technologies provide lower cost electricity, enhanced energy storage and transmission infrastructure come at a cost for managing renewable intermittency. Energy storage systems vary in characteristics and costs, and future grids will incorporate multiple technologies, yet the optimal combination of storage technologies and the role of interconnectors in alleviating storage needs are not widely explored. This study focuses on optimal generation-storage capacity requirements to elucidate associated investments. We propose a multitimescale storage solution consisting of three storage categories and an …

Asthmatic Patients With High Serum Amyloid A Have Proinflammatory Hdl: Implications For Augmented Systemic And Airway Inflammation., Xianglan Yao, Maryann Kaler, Xuan Qu, Rama Satyanarayana Raju Kalidhindi, Denis Sviridov, Amaury Dasseux, Eric Barr, Karen Keeran, Kenneth R. Jeffries, Zu-Xi Yu, Meixia Gao, Scott Gordon, Amisha V. Barochia, Joni Mills, Shahid Shahid, Nargues A. Weir, Or Kalchiem-Dekel, Patricia Theard, Martin P. Playford, Mario Stylianou, Wendy Fitzgerald, Alan T. Remaley, Stewart J. Levine

Physiology Faculty Publications

RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity.

OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory.

METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice.

RESULTS: …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

C2h2 Zinc Finger Transcription Factors Associated With Hemoglobinopathies, Xing Zhang, Fangfang Xia, Xiaotian Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin …

Mitochondrial Regulation Of Gpx4 Inhibition-Mediated Ferroptosis In Acute Myeloid Leukemia, Hiroki Akiyama, Ran Zhao, Lauren B Ostermann, Ziyi Li, Matthew Tcheng, Samar J Yazdani, Arman Moayed, Malcolm L Pryor, Sandeep Slngh, Natalia Baran, Edward Ayoub, Yuki Nishida, Po Yee Mak, Vivian R Ruvolo, Bing Z Carter, Aaron D Schimmer, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Resistance to apoptosis in acute myeloid leukemia (AML) cells causes refractory or relapsed disease, associated with dismal clinical outcomes. Ferroptosis, a mode of non-apoptotic cell death triggered by iron-dependent lipid peroxidation, has been investigated as potential therapeutic modality against therapy-resistant cancers, but our knowledge of its role in AML is limited. We investigated ferroptosis in AML cells and identified its mitochondrial regulation as a therapeutic vulnerability. GPX4 knockdown induced ferroptosis in AML cells, accompanied with characteristic mitochondrial lipid peroxidation, exerting anti-AML effects in vitro and in vivo. Electron transport chains (ETC) are primary sources of coenzyme Q

Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Hemorrhagic Stroke, Muhammad E Haque, Seth B Boren, James Mills, Kerry G Schneider, Maria Parekh, Stuart M Fraser, Ivo Bach, Praveen Hariharan, Pamela J Zelnick, Felix S Guerra Castanon, Asim Naveed, Muhammad Tariq, Octavio D Arevalo, Khader M Hasan, Miguel Escobar, Xiurong Zhao, Clark Sitton, Ponnada A Narayana, James C Grotta, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, …

New Horizons In Hyperpolarized13c Mri, Myriam M Chaumeil, James A Bankson, Kevin M Brindle, Shdema Epstein, Ferdia A Gallagher, Martin Grashei, Caroline Guglielmetti, Joshua D Kaggie, Kayvan R Keshari, Stephan Knecht, Christoffer Laustsen, Andreas B Schmidt, Daniel Vigneron, Yi-Fen Yen, Franz Schilling

Faculty, Staff and Student Publications

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons …

E-Cadherin Loss Drives Diffuse-Type Gastric Tumorigenesis Via Ezh2-Mediated Reprogramming, Gengyi Zou, Yuanjian Huang, Shengzhe Zhang, Kyung-Pil Ko, Bongjun Kim, Jie Zhang, Vishwa Venkatesan, Melissa P Pizzi, Yibo Fan, Sohee Jun, Na Niu, Huamin Wang, Shumei Song, Jaffer A Ajani, Jae-Il Park

Faculty, Staff and Student Publications

Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC is linked to CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic DGAC tumorigenesis remains elusive. We discovered CDH1 inactivation in a subset of DGAC patient tumors. Analyzing single-cell transcriptomes in malignant ascites, we identified two DGAC subtypes: DGAC1 (CDH1 loss) and DGAC2 (lacking immune response). DGAC1 displayed distinct molecular signatures, activated DGAC-related pathways, and an abundance of exhausted T cells in ascites. Genetically engineered murine gastric organoids showed that Cdh1 knock-out (KO), KrasG12D, Trp53 KO (EKP) accelerates tumorigenesis with immune evasion …

Protective Effects Of The Postbiotic Lactobacillus Plantarum Md35 On Bone Loss In An Ovariectomized Mice Model, Ju-Yeong Myeong, Hye-Yeon Jung, Hyo-Seok Chae, Hyang Hyun Cho, Don-Kyu Kim, You-Jee Jang, Jae-Il Park

Faculty, Staff and Student Publications

Postmenopausal osteoporosis is caused by estrogen deficiency, which impairs bone homeostasis, resulting in increased osteoclastic resorption without a corresponding increase in osteoblastic activity. Postbiotics have several therapeutic properties, including anti-obesity, anti-diabetic, anti-inflammatory, and anti-osteoporotic effects. However, the beneficial effects of the postbiotic MD35 of Lactobacillus plantarum on bone have not been studied. In this study, we demonstrated that the postbiotic L. plantarum MD35, isolated from young radish water kimchi, influences osteoclast differentiation in mouse bone marrow-derived macrophage (BMM) culture. In addition, it was effective protecting against estrogen deficiency-induced bone loss in ovariectomized (OVX) mice, an animal model of postmenopausal osteoporosis. …

A Building Block Of Empathy: Establishing A Graphic Medicine Collection In An Academic Health Sciences Library., Jess King, Alison Bobal

Journal Articles: Leon S. McGoogan Health Sciences Library

To help address the well-being of the campus and contribute to empathy building amongst students pursuing careers as healthcare providers, an academic health sciences library built a graphic novel collection focused on comics that discuss medical conditions and health-related topics. The collection contains the experiences of patients, providers, and caregivers. The reader-friendly format of graphic novels provides an easy entry point for discussing empathy with health professions faculty and students. The collection has been used in the classroom during library instruction sessions, with the idea of integrating it within the curriculum.

A Mutation In Tbxt Causes Congenital Vertebral Malformations In Humans And Mice, Shuxia Chen, Yunping Lei, Yajun Yang, Chennan Liu, Lele Kuang, Li Jin, Richard H Finnell, Xueyan Yang, Hongyan Wang

Faculty, Staff and Students Publications

T-box transcription factor T (TBXT; T) is required for mesodermal formation and axial skeletal development. Although it has been extensively studied in various model organisms, human congenital vertebral malformations (CVMs) involving T are not well established. Here, we report a family with 15 CVM patients distributed across 4 generations. All affected individuals carry a heterozygous mutation, T c.596A>G (p.Q199R), which is not found in unaffected family members, indicating co-segregation of the genotype and phenotype. In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity, but reduces its transcriptional activity compared to the wild-type. …

The Role Of Epigenetic Mechanisms In The Long-Term Effects Of Early-Life Adversity And Mother-Infant Relationship On Physiology And Behavior Of Offspring In Laboratory Rats And Mice, Olga V Burenkova, Elena L Grigorenko

Faculty, Staff and Students Publications

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of …

Monophosphoryl Lipid A-Based Adjuvant To Promote The Immunogenicity Of Multivalent Meningococcal Polysaccharide Conjugate Vaccines, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a central role in this process. Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand-based adjuvant would improve their immunogenicity. …

Bringing Proteomics To Bear On Male Fertility: Key Lessons, Rachel Parkes, Thomas X Garcia

Faculty, Staff and Students Publications

Introduction: Male infertility is a major public health concern globally. Proteomics has revolutionized our comprehension of male fertility by identifying potential infertility biomarkers and reproductive defects. Studies comparing sperm proteome with other male reproductive tissues have the potential to refine fertility diagnostics and guide infertility treatment development.

Areas covered: This review encapsulates literature using proteomic approaches to progress male reproductive biology. Our search methodology included systematic searches of databases such as PubMed, Scopus, and Web of Science for articles up to 2023. Keywords used included 'male fertility proteomics,' 'spermatozoa proteome,' 'testis proteomics,' 'epididymal proteomics,' and 'non-hormonal male contraception.' Inclusion criteria …

Sensory Experiences Questionnaire Unravels Differences In Sensory Profiles Between Mecp2-Related Disorders, Bernhard Suter, Davut Pehlivan, Muharrem Ak, Holly K Harris, Ariel M Lyons-Warren

Faculty, Staff and Students Publications

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 …

The Power And Promise Of Patient-Derived Xenografts Of Human Breast Cancer, Michael T Lewis, Carlos Caldas

Faculty, Staff and Students Publications

In 2016, a group of researchers engaged in the development of patient-derived xenografts (PDXs) of human breast cancer provided a comprehensive review of the state of the field. In that review, they summarized the clinical problem that PDXs might address, the technical approaches to their generation (including a discussion of host animals and transplant conditions tested), and presented transplantation success (take) rates across groups and across transplantation conditions. At the time, there were just over 500 unique PDX models created by these investigators representing all three clinically defined subtypes (ER

Temporary Peripheral Nerve Stimulation For The Treatment Of Greater Occipital Neuralgia, Royce Copeland, Angela Nwankwo, Emanuel Narcis Husu

Faculty, Staff and Students Publications

Background: Greater occipital neuralgia (GON), a cause of chronic headaches, can be debilitating and vastly affect one's quality of life. Recent strides in comprehending the pathophysiology of GON and the ongoing evolution of approaches to the condition's treatment have led to the pursuit of more effective interventions. Among these, temporary peripheral nerve stimulation (PNS) devices have surfaced as an avenue for management, presenting a minimally invasive yet highly efficient alternative in treating other chronic pain conditions. This study discusses a case of GON successfully managed with temporary (60-day) PNS.

Case report: A 35-year-old man presented with a nearly 8-month history …

The Satb1-Mir22-Gba Axis Mediates Glucocerebroside Accumulation Inducing A Cellular Senescence-Like Phenotype In Dopaminergic Neurons, Taylor Russo, Benjamin Kolisnyk, Aswathy B S, Jonathan Plessis-Belair, Tae Wan Kim, Jacqueline Martin, Jason Ni, Jordan A Pearson, Emily J Park, Roger B Sher, Lorenz Studer, Markus Riessland

Faculty, Staff and Students Publications

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype …

A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. …

Lac-Phe Mediates The Effects Of Metformin On Food Intake And Body Weight, Shuke Xiao, Veronica L Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D Taylor, Xiuqing Guo, Mark O Goodarzi, Alexis C Wood, Yii-Der Ida Chen, Leslie A Lange, Stephen S Rich, Jerome I Rotter, Clary B Clish, Usman A Tahir, Robert E Gerszten, Mark D Benson, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the …

Cholesterol 25-Hydroxylase Mediates Neuroinflammation And Neurodegeneration In A Mouse Model Of Tauopathy, Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of …

Brain High-Throughput Multi-Omics Data Reveal Molecular Heterogeneity In Alzheimer's Disease, Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari

2020-Current year OA Pubs

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, …

Neutrophils Are Indispensable For Adverse Cardiac Remodeling In Heart Failure, Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu, Gregg Rokosh

2020-Current year OA Pubs

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both …

Prevotella Copri And Microbiota Members Mediate The Beneficial Effects Of A Therapeutic Food For Malnutrition, Hao-Wei Chang, Evan M Lee, Yi Wang, Cyrus Zhou, Kali M Pruss, Suzanne Henrissat, Robert Y Chen, Clara Kao, Matthew C Hibberd, Hannah M Lynn, Daniel M Webber, Marie Crane, Jiye Cheng, Ye Chen, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics …

Reliability And Validity Of Smartphone Cognitive Testing For Frontotemporal Lobar Degeneration, Adam M Staffaroni, Nupur Ghoshal, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.

OBJECTIVE: To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. …

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Influenza Incidence, Lineages, And Vaccine Effectiveness Estimates In Lima, Peru, 2023, Juan Gonzalo Acevedo-Rodriguez, Carlos Zamudio, Noah Kojima, Fiorella Krapp, Pablo Tsukayama, Victor Giancarlo Sal Y Rosas Celi, Dante Baldeon, Carmen Stefany Neciosup-Vera, Carlos Medina, Elsa Gonzalez-Lagos, Laura Castro, Ashley Fowlkes, Eduardo Azziz-Baumgartner, Eduardo Gotuzzo

Faculty, Staff and Student Publications

No abstract provided.

Does A Reduction In Receiving Assistance With Daily Activities Among Older Adults In Mexico Indicate An Increase In Unmet Needs Or A Decrease In Needs For Care?, Brian Downer, Rafael Samper-Ternent, Philip Cantu, Matthew Miller, Rebeca Wong

Faculty, Staff and Student Publications

OBJECTIVES: The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

METHODS: We selected Mexican Health and Aging Study participants aged 60-76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if …