Physical Sciences and Mathematics Commons^™

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Using Low-Dose Radiation To Potentiate The Effect Of Induction Chemotherapy In Head And Neck Cancer: Results Of A Prospective Phase 2 Trial, Susanne M. Arnold, Mahesh Kudrimoti, Emily V. Dressler, John F. Gleason, Natalie L. Silver, William F. Regine, Joseph Valentino

Internal Medicine Faculty Publications

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN).

Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m²) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

An Interactive Videogame Designed To Improve Respiratory Navigator Efficiency In Children Undergoing Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Jonathan D. Grabau, Kristin N. Andres, Moriel H. Vandsburger, David K. Powell, Vincent L. Sorrell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Advanced cardiovascular magnetic resonance (CMR) acquisitions often require long scan durations that necessitate respiratory navigator gating. The tradeoff of navigator gating is reduced scan efficiency, particularly when the patient’s breathing patterns are inconsistent, as is commonly seen in children. We hypothesized that engaging pediatric participants with a navigator-controlled videogame to help control breathing patterns would improve navigator efficiency and maintain image quality.

Methods: We developed custom software that processed the Siemens respiratory navigator image in real-time during CMR and represented diaphragm position using a cartoon avatar, which was projected to the participant in the scanner as visual feedback. The …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Left And Right Ventricular Dyssynchrony And Strains From Cardiovascular Magnetic Resonance Feature Tracking Do Not Predict Deterioration Of Ventricular Function In Patients With Repaired Tetralogy Of Fallot, Linyuan Jing, Gregory J. Wehner, Jonathan D. Suever, Richard Charnigo, Sudad Alhadad, Evan Stearns, Dimitri Mojsejenko, Christopher M. Haggerty, Kelsey Hickey, Anne Marie Valente, Tal Geva, Andrew J. Powell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF.

Methods: A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, > 6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Partner Interfering Behaviors Affecting Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

Obstetrics and Gynecology Faculty Publications

Objective: Because partners are an important and unpaid resource in cancer care, understanding how destructive, controlling or interfering partner behaviors influence women's cancer care may be particularly relevant for health care providers seeking to provide cancer care and enhance recovery. Using a new measure of partner interfering behaviors in cancer care (PIB-C), we investigated whether women with a recent cancer diagnosis who additionally endorsed any PIB-C would report (a) more symptoms of depression and stress, and (b) lower Functional Assessment of Cancer Therapy (FACT-G) and lower Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-SP) scale scores indicating poorer quality of …

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …

Alzheimer's Biomarkers Are Correlated With Brain Connectivity In Older Adults Differentially During Resting And Task States, Yang Jiang, Haiqing Huang, Erin Abner, Lucas S. Broster, Gregory A. Jicha, Frederick A. Schmitt, Richard Kryscio, Anders H. Andersen, David Powell, Linda J. Van Eldik, Brian T. Gold, Peter T. Nelson, Charles D. Smith, Mingzhou Ding

Behavioral Science Faculty Publications

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ₄₂ and pTau₁₈₁), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ …

Salvage Brachytherapy For Biochemically Recurrent Prostate Cancer Following Primary Brachytherapy, John M. Lacy, William A. Wilson, Raevti Bole, Li Chen, Ali S. Meigooni, Randall G. Rowland, William H. St. Clair

Urology Faculty Publications

Purpose. In this study, we evaluated our experience with salvage brachytherapy after discovery of biochemical recurrence after a prior brachytherapy procedure. Methods and Materials. From 2001 through 2012 twenty-one patients treated by brachytherapy within University of Kentucky or from outside centers developed biochemical failure and had no evidence of metastases. Computed tomography (CT) scans were evaluated; patients who had an underseeded portion of their prostate were considered for reimplantation. Results. The majority of the patients in this study (61.9%) were low risk and median presalvage PSA was 3.49 (range 17.41–1.68). Mean follow-up was 61 months. At last follow-up after reseeding, …