Medicine and Health Sciences Commons^™

Genome-Wide Dna Methylation Profiling In Human Breast Tissue By Illumina Truseq Methyl Capture Epic Sequencing And Infinium Methylationepic Beadchip Microarray, Nan Lin, Jinpeng Liu, James Castle, Jun Wan, Aditi Shendre, Yunlong Liu, Chi Wang, Chunyan He

Markey Cancer Center Faculty Publications

A newly-developed platform, the Illumina TruSeq Methyl Capture EPIC library prep (TruSeq EPIC), builds on the content of the Infinium MethylationEPIC Beadchip Microarray (EPIC-array) and leverages the power of next-generation sequencing for targeted bisulphite sequencing. We empirically examined the performance of TruSeq EPIC and EPIC-array in assessing genome-wide DNA methylation in breast tissue samples. TruSeq EPIC provided data with a much higher density in the regions when compared to EPIC-array (~2.74 million CpGs with at least 10X coverage vs ~752 K CpGs, respectively). Approximately 398 K CpGs were common and measured across the two platforms in every sample. Overall, there …

Meta-Analysis Of Cyathostomin Species-Specific Prevalence And Relative Abundance In Domestic Horses From 1975-2020: Emphasis On Geographical Region And Specimen Collection Method, Jennifer L. Bellaw, Martin K. Nielsen

Maxwell H. Gluck Equine Research Center Faculty Publications

BACKGROUND: Cyathostomins infect virtually all horses, and concomitant infections with 10 or more species per horse is standard. Species-specific knowledge is limited, despite potential species bias in development of disease and anthelmintic resistance. This is the first meta-analysis to examine effects of geographical region and cyathostomin collection method on reported composition of cyathostomin communities.

METHODS: Thirty-seven articles published in English in 1975 or later, in which adults of individual species were systematically enumerated, were included. Seven regions; North America, South America, eastern Europe, western Europe, northern Europe, southern Africa, and Oceania, and three cyathostomin collection methods; (i) standard necropsy recovery …

Clinical Application Of Oncolytic Viruses: A Systematic Review, Mary Cook, Aman Chauhan

Internal Medicine Faculty Publications

Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic …

The Srg Rat, A Sprague-Dawley Rag2/Il2rg Double-Knockout Validated For Human Tumor Oncology Studies, Fallon K. Noto, Jaya Sangodkar, Bisoye Towobola Adedeji, Sam Moody, Christopher B. Mcclain, Ming Tong, Eric Ostertag, Jack Crawford, Xiaohua Gao, Lauren Hurst, Caitlin M. O'Connor, Erika N. Hanson, Sudeh Izadmehr, Rita Tohmé, Jyothsna Narla, Kristin Lesueur, Kajari Bhattacharya, Amit Rupani, Marwan K. Tayeh, Jeffrey W. Innis, Matthew D. Galsky, B. Mark Evers, Analisa Difeo, Goutham Narla, Tseten Y. Jamling

Markey Cancer Center Faculty Publications

We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. This model has been tested and validated for use in oncology (SRG OncoRat®). The SRG rat demonstrates efficient tumor take rates and growth kinetics with different human cancer cell lines and PDXs. Although multiple immunodeficient rodent strains are available, some important human cancer cell lines exhibit poor tumor growth and high variability in those models. The VCaP prostate cancer model is one such cell line that engrafts unreliably and grows irregularly in …

Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We …

Development And Implementation Of An Influenza Point-Of-Care Testing Service In A Chain Community Pharmacy Setting, Rachel Hardin, Pheli Roberts, Brooke Hudspeth, Angela Tracy, Lauren Baldwin, Michael Raque, Clark D. Kebodeaux

Pharmacy Practice and Science Faculty Publications

Point-of-care testing is becoming increasingly commonplace in community pharmacy settings. These tests are often used in the management of chronic disease, such as blood sugar, hemoglobin A1c and lipid levels, but can also be used for acute conditions such as influenza infection and group A streptococcus pharyngitis. When used for these acute infections, point-of-care tests can allow for pharmacist-initiated treatment. In this study, an influenza point-of-care testing service was developed and implemented in a chain community pharmacy setting and a retrospective review was conducted to assess the service. Of patients tested, 29% tested positive for influenza A and/or B; 92% …

The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett

Pharmaceutical Sciences Faculty Publications

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the …

Microglia Prevent Beta-Amyloid Plaque Formation In The Early Stage Of An Alzheimer's Disease Mouse Model With Suppression Of Glymphatic Clearance, Weixi Feng, Yanli Zhang, Ze Wang, Hanrong Xu, Ting Wu, Charles Marshall, Junying Gao, Ming Xiao

Physical Therapy Faculty Publications

BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer's disease (AD) are currently unknown.

METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4^−/−) mice, and AQP4^−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein …

Measuring The Spread Of Covid-19 In Kentucky: Do We Have The Right Data?, Kenneth R. Troske, Paul A. Coomes

Institute for the Study of Free Enterprise Working Papers

We examine various measures of COVID-19 infections, hospitalizations and deaths, with an emphasis on data for Kentucky. We find that: Data on the number of new reported cases of the disease obtained from convenience samples (as opposed to representative random samples) is an inaccurate measure of the spread of the disease in the State. Using CDC data and national studies, it appears that there were ten times the number of infections in March than reported for Kentucky at the time and by September the State is still capturing only one out of two people infected.

A better measure of new …

Imaging Data On Characterization Of Retinal Autofluorescent Lesions In A Mouse Model Of Juvenile Neuronal Ceroid Lipofuscinosis (Cln3 Disease), Qing Jun Wang, Kyung Sik Jung, Kabhilan Mohan, Mark E. Kleinman

Ophthalmology and Visual Science Faculty Publications

Juvenile neuronal ceroid lipofuscinosis (JNCL, aka. juvenile Batten disease or CLN3 disease), a lethal pediatric neurodegenerative disease without cure, often presents with vision impairment and characteristic ophthalmoscopic features including focal areas of hyper-autofluorescence. In the associated research article “Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retinal pigment epithelium” (Zhong et al., 2020) [1], we reported ophthalmoscopic observations of focal autofluorescent lesions or puncta in the Cln3^Δex7/8 mouse retina at as young as 8 month old. In this data article, we performed differential interference contrast and …

Balloon Atrial Septostomy As Initial Therapy In Pediatric Pulmonary Hypertension, Paul J. Critser, Patrick D. Evers, Eimear Mcgovern, Michelle Cash, Russel Hirsch

Pediatrics Faculty Publications

Balloon atrial septostomy is a palliative procedure currently used to bridge medically refractory pulmonary hypertension patients to lung transplantation. In the current report, we present balloon atrial septostomy as an initial therapy for high-risk pediatric pulmonary hypertension patients at our institution. Nineteen patients with median age of 4.3 years (range 0.1-14.3 years) underwent balloon atrial septostomy during initial admission for pulmonary hypertension. There were no procedural complications or deaths within 24 h of balloon atrial septostomy. Patients were followed for a median of 2.6 years (interquartile range 1.0-4.8 years). Three (16%) patients died, 3 (16%) underwent lung transplantation, and 1 …

A Thorough Analysis And Categorization Of Bacterial Interrupted Adenylation Domains, Including Previously Unidentified Families, Taylor A. Lundy, Shogo Mori, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Interrupted adenylation (A) domains are key to the immense structural diversity seen in the nonribosomal peptide (NRP) class of natural products (NPs). Interrupted A domains are A domains that contain within them the catalytic portion of another domain, most commonly a methylation (M) domain. It has been well documented that methylation events occur with extreme specificity on either the backbone (N-) or side chain (O- or S-) of the amino acid (or amino acid-like) building blocks of NRPs. Here, through taxonomic and phylogenetic analyses as well as multiple sequence alignments, we evaluated the similarities and …

Cardioplastic Approach To Omental Flap Coverage For Severe Aortic Root Infections In The Opioid Era, Alisha R. Bonaroti, R. Wesley Edmunds, Ryan C. Decoster, James Y. Liau, Michael E. Sekela, Henry C. Vasconez

Surgery Faculty Publications

Aortic root abscesses are severe sequelae of endocarditis that clinically manifest as life-threatening infection. As the opioid epidemic continues to yield a national crisis, the incidence and severity of this disease process have increased. Reconstruction of the aortic root is a challenging undertaking and carries the risk of recurrent infection. The omentum has an established reputation as a reliable flap in thoracic reconstruction, given its amorphous form and immunogenic properties, but it has not been utilized for aortic root infections. We present a novel indication for the omental flap using a cardioplastic approach in coverage of aortic root reconstruction. Four …

From Leads To Leadless: A Convoluted Journey, Vipin Dulam, Joshua M. Cooper, Chethan Gangireddy, Mohammed A. Kashem, Yoshiya Toyoda, Suresh Keshavamurthy

Surgery Faculty Publications

No abstract provided.

Sod2 Deficiency In Cardiomyocytes Defines Defective Mitochondrial Bioenergetics As A Cause Of Lethal Dilated Cardiomyopathy, Sudha Sharma, Susmita Bhattarai, Hosne Ara, Grace Sun, Daret K. St. Clair, Md Shenuarin Bhuiyan, Christopher Kevil, Megan N. Watts, Paari Dominic, Takahiko Shimizu, Kevin J. Mccarthy, Hong Sun, Manikandan Panchatcharam, Sumitra Miriyala

Toxicology and Cancer Biology Faculty Publications

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2^•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the …

Haiti's Hiv Surveillance System: Past, Present, And Future, Chris Delcher, Ermane G. Robin, Daniella Myriam Pierre

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Nlrp3 Inflammasome Signaling Regulates The Homing And Engraftment Of Hematopoietic Stem Cells (Hspcs) By Enhancing Incorporation Of Cxcr4 Receptor Into Membrane Lipid Rafts, Mateusz Adamiak, Ahmed K. Abdel-Latif, Kamila Bujko, Arjun Thapa, Krzysztof Anusz, Michał Tracz, Katarzyna Brzezniakiewicz-Janus, Janina Ratajczak, Magda Kucia, Mariusz Z. Ratajczak

Internal Medicine Faculty Publications

Fast and efficient homing and engraftment of hematopoietic stem progenitor cells (HSPCs) is crucial for positive clinical outcomes from transplantation. We found that this process depends on activation of the Nlrp3 inflammasome, both in the HSPCs to be transplanted and in the cells in the recipient bone marrow (BM) microenvironment. For the first time we provide evidence that functional deficiency in the Nlrp3 inflammasome in transplanted cells or in the host microenvironment leads to defective homing and engraftment. At the molecular level, functional deficiency of the Nlrp3 inflammasome in HSPCs leads to their defective migration in response to the major …

Current Role Of Laser Interstitial Thermal Therapy In The Treatment Of Intracranial Tumors, Farhan A. Mirza, Rida Mitha, Muhammad Shahzad Shamim

Neurosurgery Faculty Publications

Laser interstitial thermal therapy (LITT) is gaining popularity in the treatment of both primary and secondary intracranial tumors. The goal of LITT is to deliver thermal energy in a predictable, controlled, and minimally invasive fashion. It can be particularly valuable in patients with recurrent tumors who, due to previous radiation or surgery, may have a potentially higher risk of wound breakdown or infection with repeat craniotomy. Deep-seated lesions that are often inaccessible through open approaches (thalamus, hypothalamus, mesial basal temporal lobe, brainstem) may also be suitable targets. The experience and data published thus far on this modality is limited but …

Importation Of Macrocyclic Lactone Resistant Cyathostomins On A Us Thoroughbred Farm, Martin K. Nielsen, M. Banahan, R. M. Kaplan

Maxwell H. Gluck Equine Research Center Faculty Publications

Anthelmintic resistance in equine cyathostomins is both widespread and highly prevalent in the benzimidazole and tetrahydropyrimidine classes; however, reports of resistance to macrocyclic lactone (ML) drugs are sparse and sporadic. This study reports a case of clear ML resistance in a group of Thoroughbred yearlings imported from Ireland to the US in 2019. Fecal egg count reduction (FECR) following ivermectin administered in February 2020 demonstrated 100% reduction in the US bred yearlings, but 93.5%, 70.5%, and 74.5% reduction in three groups of the imported yearlings. The two former groups were then retreated with ivermectin, yielding FECRs of 33.8% and 23.5%, …

Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff

Radiology Faculty Publications

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained …

Tdp-43 Mediated Blood-Brain Barrier Permeability And Leukocyte Infiltration Promote Neurodegeneration In A Low-Grade Systemic Inflammation Mouse Model, Frank Zamudio, Anjanet R. Loon, Shayna Smeltzer, Khawla Benyamine, Nanda K. Navalpur Shanmugam, Nicholas J. F. Stewart, Daniel C. Lee, Kevin Nash, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.

METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected …

Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, …

Neutrophil: A New Player In Metastatic Cancers, Mengyue Wu, Mutian Ma, Zhenya Tan, Hong Zheng, Xia Liu

Toxicology and Cancer Biology Faculty Publications

The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, …

Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a …

Repurposing Anti-Inflammasome Nrtis For Improving Insulin Sensitivity And Reducing Type 2 Diabetes Development, Jayakrishna Ambati, Joseph Magagnoli, Hannah Leung, Shao-Bin Wang, Chris A. Andrews, Dongxu Fu, Akshat Pandey, Srabani Sahu, Siddharth Narendran, Shuichiro Hirahara, Shinichi Fukuda, Jian Sun, Lekha Pandya, Meenakshi Ambati, Felipe Pereira, Akhil Varshney, Tammy Cummings, James W. Hardin, Babatunde Edun, Charles L. Bennett, Kameshwari Ambati, Benjamin J. Fowler, Nagaraj Kerur, Christian Röver, Norbert Leitinger, Brian C. Werner, Joshua D. Stein, S. Scott Sutton, Bradley D. Gelfand

Ophthalmology and Visual Science Faculty Publications

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.

Organic Field-Effect Transistors As Flexible, Tissue-Equivalent Radiation Dosimeters In Medical Applications, Andrew M. Zeidell, Tong Ren, David S. Filston, Hamna F. Iqbal, Emma Holland, J. Daniel Bourland, John E. Anthony, Oana D. Jurchescu

Chemistry Faculty Publications

Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors …

Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.

Microglial-Associated Responses To Comorbid Amyloid Pathology And Hyperhomocysteinemia In An Aged Knock-In Mouse Model Of Alzheimer's Disease, David J. Braun, Edgardo R. Dimayuga, Josh M. Morganti, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies.

METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of …

Ethics And Economics Of The Covid-19 Pandemic In The United States, Peter Hilsenrath, Tyrone F. Borders

Health Management and Policy Faculty Publications

The Covid-19 experience provides a natural experiment in personal and social ethics. Difficult decisions are routinely made to optimize lives and livelihoods. This commentary provides background and insight into the ethical and economic foundations underpinning dilemmas of this historic pandemic.

Neurotropic Lineage Iii Strains Of Listeria Monocytogenes Disseminate To The Brain Without Reaching High Titer In The Blood, Taylor E. Senay, Jessica L. Ferrell, Filip G. Garrett, Taylor M. Albrecht, Jooyoung Cho, Katie L. Alexander, Tanya Myers-Morales, Olivia F. Grothaus, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain …