Digital Commons Network^™

Myosin Xva Isoforms Participate In The Mechanotransduction-Dependent Remodeling Of The Actin Cytoskeleton In Auditory Stereocilia, Ana I. López-Porras, Ava M. Kruse, Mark T. Mcclendon, A. Catalina Vélez-Ortega

Neurology Faculty Publications

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter ‘transducing’ stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms, given their known roles in the regulation of stereocilia dimensions during hair …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …

Alternatives To Dental Opioid Prescribing After Tooth Extraction (Adopt), Douglas R. Oyler, Philip M. Westgate, Sharon L. Walsh, Jennifer Dolly Prothro, Craig S. Miller, Monica F. Roberts, Patricia R. Freeman, Hannah K. Knudsen, Maggie Lang, Enif Dominguez-Fernandez, Marcia V. Rojas-Ramirez

Biostatistics Faculty Publications

Background: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. Methods: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12–25 years …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

Tissue Plasminogen Activator Associated Pulmonary Hemorrhage In Patient With Acta2-Associated Arteriopathy, Travis G. Hughes, Mark A. Wurth, Mary Burchett Sheppard

Saha Cardiovascular Research Center Faculty Publications

Pulmonary hemorrhage after administration of tissue plasminogen activator (tPA) is a rare complication. We present a 15- year-old boy with a heterozygous pathogenic variant in ACTA2 who presented with right brachial artery aneurysm thrombosis treated initially with tPA, resulting in pulmonary hemorrhage. We hypothesize that the underlying pulmonary abnormalities caused by the pathogenic ACTA2 variant may be a risk factor for pulmonary hemorrhage after tPA administration. (J Vasc Surg Cases Innov Tech 2024;10:101558.)

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Nutraceutical Supplement Mitigates Insulin Resistance In Horses With A History Of Insulin Dysregulation During A Challenge With A High-Starch Diet, Caroline Loos, Annette Castelein, Eric Vanzant, Emma Adam, Kyle R. Mcleod

Animal and Food Sciences Faculty Publications

Insulin dysregulation (ID) is associated with an increased risk of laminitis which often necessitates the need for clinical intervention. To test the contention that the prophylactic supplementation of nutraceuticals could mitigate ID in susceptible horses, 16 mature horses with a history of ID were supplemented with either the placebo (n = 8) or nutraceutical (n = 8) once daily. Horses were housed in dry lots with ad libitum access to grass hay and fed a concentrate twice daily to provide 0.5 g starch/kg BW/meal. A combined glucose–insulin tolerance test was performed on all horses before and after 4 weeks of …

The Endocannabinoid System In Bovine Tissues, Coral Kent-Dennis, James L. Klotz

Animal and Food Sciences Faculty Publications

Background: The endocannabinoid system (ECS) is highly integrated with seemingly all physiological and pathophysiological processes in the body. There is increasing interest in utilizing bioactive plant compounds, for promoting health and improving production in livestock. Given the established interaction between phytochemicals and the ECS, there are many opportunities for identification and development of therapies to address a range of diseases and disorders. However, the ECS has not been thoroughly characterized in cattle, especially in the gastrointestinal tract. The objective of this study was to characterize the distribution and transcriptional abundance of genes associated with the endocannabinoid system in bovine tissues. …

Prevalent Atherosclerotic Cardiovascular Disease Among Veterans By Sexual Orientation, Carl G. Streed, Meredith S. Duncan, Kory R. Heier, T. Elizabeth Workman, Lauren B. Beach, Billy A. Caceres, John R. O’Leary, Melissa Skanderson, Joseph L. Goulet

Biostatistics Faculty Publications

BACKGROUND: Seven million lesbian, gay, and bisexual (LGB) adults will be aged >50 years by 2030; assessing and addressing their risk for cardiovascular disease is critical. METHODS AND RESULTS: We analyzed a nationwide cohort using the Veterans Health Administration data. Sexual orientation (SO) was classified via a validated natural language processing algorithm. Prevalent atherosclerotic cardiovascular disease (ASCVD) (history of acute myocardial infarction, ischemic stroke, or revascularization) was identified via International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and ICD-10) codes. The index date was the date of the first primary care appointment on or after October 1, 2009. We …

Harmonizing Data Across The Accelerating Colorectal Cancer Screening And Follow-Up Through Implementation Science (Accsis) Program To Enhance Data Quality And Promote Data Sharing., Sujha Subramanian, Sarah Kobrin, Sonja Hoover, Sylvia Tan, Alison T. Brenner, Janis E. Campbell, Jennifer Hatcher, Bin Huang, Madeleine Jones, Erin S. Kenzie, Helen Lam, David Liebovitz, Shiraz I. Mishra, Meghan C. O'Leary, Kristine N. Ortwine, V. Shane Pankratz, Electra D. Paskett, Michael Pennell, Amanda F. Petrik, Scott Roesch

Internal Medicine Faculty Publications

BACKGROUND: The purpose of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) Program, a Cancer Moonshot℠ Initiative, is to support research to build the evidence base on multilevel interventions that increase rates of colorectal cancer screening, follow-up, and referral to care to address disparities in colorectal cancer screening. The National Cancer Institute funded eight Research Projects to implement multilevel interventions to improve colorectal cancer screening among communities who traditionally have been medically underserved. To analyze the impact of ACCSIS across Research Projects, the consortium developed a set of common data elements. The purpose of this paper is …

Table B: Impacts Of Utensil Use In Preparation, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Impact Of State Abortion Policies On Family Medicine Practice And Training After Dobbs V Jackson Women’S Health Organization, Karen L. Roper, Sarah Jane Robbins, Philip Day, Grace Shih, Neelima Kale

UK CARES Faculty Publications

PURPOSE The Dobbs v Jackson Women’s Health Organization (Dobbs) Supreme Court decision revoked the constitutional right to abortion. Now, restrictive state abortion laws may con- tribute to the shortage and strain already felt in primary care practice, especially related to the provision of reproductive health care. The purpose of this study is to evaluate perceived impacts of state abortion legislation on family medicine clinicians’ practice and medical edu- cation regarding reproductive health care.

METHODS Ten questions were added to the 2022 Council of Academic Family Medicine Educational Research Alliance general membership survey to evaluate impact on relevant themes in reproductive …

Forage News [2024-11], University Of Kentucky

Forage News

No abstract provided.

Enlarged Perivascular Space Burden Predicts Declines In Cognitive And Functional Performance, Timothy Justin Libecap, Colleen A. Pappas, Christopher E. Bauer, Valentinos Zachariou, Flavius D. Raslau, Brian T. Gold

Neurology Faculty Publications

Introduction: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline.

Methods: 83 community-dwelling, older adults (aged 56–86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD …

Effectiveness Of Auricular Acupressure In Managing Sleep Quality, Mood, And Quality Of Life In Parents Of Children With Cancer: A Pilot Randomized Controlled Trial, Yi-Chien Chiang, Shih-Hsiang Chen, Debra K. Moser, Yu-Chuan Wen, Yu-Ting Ling, Ya-Chu Hsiao

UK CARES Faculty Publications

Objective: This pilot study aimed to assess the feasibility and effectiveness of an auricular acupressure intervention on sleep quality, mood state, and quality of life (QOL) among parents of children with cancer.

Methods: Thirty-five parents were assigned to three-weeks intervention in an active auricular acupressure group (AAG) or a sham auricular acupressure group (SAG). Feasibility was assessed by adherence to the acupressure protocol. Outcomes were measured using the Pittsburgh Sleep Quality Index for sleep quality, the Profile of Mood States for mood, and the QOL short form for QOL. The data were analyzed using generalized estimating equations to identify changes …

Coffee Beans, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Creamer, Non-Dairy, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Tea Infusion, Unspecified Tea Type, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Puer Tea Infusion, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Energy, Isotonic, Sports, And Nutritional Drinks, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Butter, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Sugar, Syrup And Molasses, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Oils, Fats, And Their Products, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Pepper, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Rice, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Cookies And Snacks, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Barley, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.