Medicine and Health Sciences Commons^™

Analysis Of Covid-19 Concerns Raised By The Construction Workforce And Development Of Mitigation Practices, Makram Bou Hatoum, Ali Faisal, Hala Nassereddine, Hadi Sarvari

Civil Engineering Faculty Publications

The coronavirus outbreak has created a global health crisis that has disrupted all industries, including the construction industry. Following the onset of the pandemic, construction workers faced and continue to face unprecedented safety and health challenges. Therefore, construction employers established new safety precautions to protect the health and safety of the workforce and minimize the spread of the virus. The new precautions followed the advice and guidelines offered by different health and safety agencies like the Occupational Safety and Health Administration (OSHA), Centers of Disease Control and Prevention (CDC), and the Associated General Contractors of America (AGC). With construction projects …

Consumption Of Diet And Nutrition Information In Digital Magazines Marketing To Latinx Women, Julie Plasencia, Clara Barajas, Jordan Hinton

Dietetics and Human Nutrition Faculty Publications

Objective: To examine the types of nutrition and health-related articles published in digital magazines directed toward Latinx women; and to examine the extent to which advertisements about food, nutrition, and weight-loss are prevalent in these media.

Design: A descriptive content analysis was completed for five digital magazines marketing to Latinx women. A total of 1,234 articles and 3,001 advertisements were examined for nutrition and health-related content.

Results: Early editions of digital magazines directed towards Latinx women included more advertisements than articles on the topics of food and health. Among the articles, very few (0-30%) included health and nutrition information that …

School Reopenings, Mobility, And Covid-19 Spread: Evidence From Texas, Charles J. Courtemanche, Anh Le, Aaron Yelowitz, Ron Zimmer

Institute for the Study of Free Enterprise Working Papers

This paper examines the effect of fall 2020 school reopenings in Texas on county-level COVID19 cases and fatalities. Previous evidence suggests that schools can be reopened safely if community spread is low and public health guidelines are followed. However, in Texas, reopenings often occurred alongside high community spread and at near capacity, likely making it difficult to meet social distancing recommendations. Using event-study models and hand-collected instruction modality and start dates for all school districts, we find robust evidence that reopening Texas schools gradually but substantially accelerated the community spread of COVID-19. Results from our preferred specification imply that school …

Medicare-Paid Naloxone: Trends In Non-Metropolitan And Metropolitan Areas, Chris Delcher, Yue Cheng, Minji Sohn, Jeffery C. Talbert, Patricia R. Freeman

Rural & Underserved Health Research Center Publications

Overview of Key Findings

• Medicare pays for the largest share (> 30%) of naloxone dispensed from retail pharmacies in non-metropolitan areas.
• Medicare-paid dispensing has grown since 2013, but from 2017-2018 dispensing growth in non-metropolitan areas slowed considerably compared to metropolitan areas (42% v 121%, respectively).
• As of 2018, the rate of naloxone dispensing to Medicare enrollees in metropolitan areas was approximately double that in non-metropolitan areas (4.9 v 2.9 per 1,000 enrollees, respectively).

Optimizing Critical Illness Recovery: Perspectives And Solutions From The Caregivers Of Icu Survivors, Carla M. Sevin, Leanne M. Boehm, Elizabeth Hibbert, Anthony J. Bastin, James C. Jackson, Joel Meyer, Tara Quasim, Rita N. Bakhru, Ashley A. Montgomery-Yates, Andrew Slack, Mary Still, Giora Netzer, Mark E. Mikkelsen, Theodore J. Iwashyna, Kimberly J. Haines, Joanne Mcpeake

Internal Medicine Faculty Publications

Objectives:
To understand the unmet needs of caregivers of ICU survivors, how they accessed support post ICU, and the key components of beneficial ICU recovery support systems as identified from a caregiver perspective.

Design:
International, qualitative study.

Subjects:
We conducted 20 semistructured interviews with a diverse group of caregivers in the United States, the United Kingdom, and Australia, 11 of whom had interacted with an ICU recovery program.

Setting:
Seven hospitals in the United States, United Kingdom, and Australia.

Interventions:
None.

Measurements and Main Results:
Content analysis was used to explore prevalent themes related to unmet needs, as well as …

Epigenome-Wide Association Study Of Kidney Function Identifies Trans-Ethnic And Ethnic-Specific Loci, Charles E. Breeze, Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. Mccartney, Rong Jiang, Amit Patki, Holly J. Kramer, James M. Eales, Laura Raffield, Leslie Lange, Ethan Lange, Peter Durda, Yongmei Liu, Russ P. Tracy, David Van Den Berg, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Mesa Multi-Omics Working Group, Kathryn L. Evans, William E. Kraus, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.

METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear …

Hemodynamic Management Of Patients With Ejection Fraction < 50% Undergoing Pulmonary Vein Ablation, Aaron B. Hesselson, Heather Hesselson

Internal Medicine Faculty Publications

There is no consensus regarding optimal methodology forblood pressure monitoring inpatients with a depressed ejection fraction undergoingcatheter ablationfor atrial fibrillation. Our goalswere to determine ifhemodynamicmanagementdifferences exist during radiofrequency ablation for atrial fibrillation in patients with and without an ejection fraction< 50%, and whether management was influenced by the utilization of invasive arterial blood pressure monitoring. This single-center trial retrospectively compared blood pressure management during catheterablation of atrial fibrillationin all patients with an ejection fraction< 50% over a 2-year span (n=44), and compared to an age-matched cohort with preserved ejection fraction ablated over the same span in time (n=44). Blood pressure was not significantly managed differently between the groups, and did not appear to be influenced by the use of invasive arterial blood pressure monitoring. Hemodynamic management is similar across the spectrum of ejection fraction, regardless of invasive arterial blood pressure monitoring, which challenges the need for invasive arterial blood pressure monitoringduringcatheter ablation ofatrial fibrillationin left ventricular systolic dysfunction.

Transcriptomic Phases Of Periodontitis Lesions Using The Nonhuman Primate Model, Jeffrey L. Ebersole, Radhakrishnan Nagarajan, Sreenatha S. Kirakodu, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12–22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n = 6049), early progression (n = 4893), and late progression …

Obstetric Patients And Healthcare Providers Perspectives To Inform Mobile App Design For Physical Activity And Weight Control During Pregnancy And Postpartum In A Rural Setting, Rachel Tinius, Cathryn Duchette, Sia Beasley, Maire Blankenship, Nancy Schoenberg

Behavioral Science Faculty Publications

Background: Mobile health technology offers the opportunity for women to engage with physical activity promotion programs without many of the barriers commonly associated with exercise during and after pregnancy (eg, childcare concerns, rigid schedules, fear of doing harm to fetus or self, access to fitness facilities, uncomfortable with body in front of others) which may be particularly useful in under-resourced rural environments. We conducted the first known study on perspectives of pregnant women, postpartum women, and obstetric healthcare providers in a rural setting on needs related to the development of a mobile app designed to increase physical activity during pregnancy …

Evaluation Of Glutaminase Expression In Prostate Adenocarcinoma And Correlation With Clinicopathologic Parameters, Zin W. Myint, Ramon C. Sun, Patrick J. Hensley, Andrew C. James, Peng Wang, Stephen E. Strup, Robert J. Mcdonald, Donglin Yan, William H. St. Clair, Derek B. Allison

Internal Medicine Faculty Publications

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, …

Informing The Pathway Of Copd Treatment (Impact) Trial: Fibrinogen Levels Predict Risk Of Moderate Or Severe Exacerbations, Dave Singh, Gerard J. Criner, Mark T. Dransfield, David M. G. Halpin, Meilan K. Han, Peter Lange, Sally Lettis, David A. Lipson, David M. Mannino, Neil Martin, Fernando J. Martinez, Bruce E. Miller, Robert Wise, Chang-Qing Zhu, David Lomas

Preventive Medicine and Environmental Health Faculty Publications

Background: Fibrinogen is the frst qualifed prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated futicasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacer‑ bations. This analysis used IMPACT trial data to examine the relationship between fbrinogen levels and exacerbation outcomes in patients with COPD.

Methods: 8094 patients with a fbrinogen assessment at Week 16 were included, baseline fbrinogen data were not measured. Post hoc analyses were performed by fbrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events …

Cross-Sectional Exploration Of Plasma Biomarkers Of Alzheimer's Disease In Down Syndrome: Early Data From The Longitudinal Investigation For Enhancing Down Syndrome Research (Life-Dsr) Study, James A. Hendrix, David C. Airey, Angela Britton, Anna D. Burke, George T. Capone, Ronelyn Chavez, Jacqueline Chen, Brian Chicoine, Alberto C. S. Costa, Jeffrey L. Dage, Eric Doran, Anna Esbensen, Casey L. Evans, Kelley M. Faber, Tatiana M. Foroud, Sarah Hart, Kelsey Haugen, Elizabeth Head, Suzanne Hendrix, Hampus Hillerstrom, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ_1-40, Aβ_1-42), and glial fibrillary acidic protein (GFAP) were undertaken with …

Disability-Free Life Expectancy Among People Over 60 Years Old By Sex, Urban And Rural Areas In Jiangxi Province, China, Shengwei Wang, Songbo Hu, Pei Wang, Yuhang Wu, Zhitao Liu, Huilie Zheng

Statistics Graduate Research

Objective: To estimate and compare age trends and the disability-free life expectancy (DFLE) of the population over 60 years old in 2018 in Jiangxi Province, China, by sex and urban–rural areas. Methods: The model life table was employed to estimate the age-specific mortality rate by sex and urban–rural areas, based on the Summary of Health Statistics of Jiangxi Province in 2018 and the Sixth National Health Service survey of Jiangxi Province. DFLE and its ratio to life expectancy (LE) were obtained by the Sullivan method. Results: In 2018, the DFLE among people over 60 is 17.157 years for men and …

Pharmacist Avoidance Or Reductions In Medical Costs In Patients Presenting The Emergency Department: Pharm-Em Study, Megan A. Rech, William Adams, Keaton S. Smetana, Payal K. Gurnani, Megan A. Van Berkel Patel, William J. Peppard, Drayton A. Hammond, Alexander H. Flannery, Pharm-Em Investigators On Behalf Of The Society Of Critical Care Medicine Clinical Pharmacy And Pharmacology Section And Endorsed By The Discovery Network

Pharmacy Practice and Science Faculty Publications

Objectives:
To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions.

Design:
A multicenter, prospective, observational study was performed between August 2018 and January 2019.

Setting:
Community and academic hospitals in the United States.

Participants:
Emergency medicine clinical pharmacists.

Interventions:
Recommendations classified into one of 38 intervention categories associated with cost avoidance.

Measurements and Main Results:
Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in …

Bone Quality In Chronic Kidney Disease Patients: Current Concepts And Future Directions – Part Ii, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution …

Effects Of Endogenous Angiotensin Ii On Abdominal Aortic Aneurysms And Atherosclerosis In Angiotensin Ii-Infused Mice, Masayoshi Kukida, Hisashi Sawada, Satoko Ohno-Urabe, Deborah A. Howatt, Jessica J. Moorleghen, Marko Poglitsch, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.

Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, And Improves Embryo Recovery In Mares, Lorenzo G. T. M. Segabinazzi, Igor F. Canisso, Giorgia Podico, Lais L. Cunha, Guilherme Novello, Michael F. Rosser, Shavanh C. Loux, Fabio S. Lima, Marco A. Alvarenga

Maxwell H. Gluck Equine Research Center Faculty Publications

Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP pre- (−48 and −24 h) and post-breeding (6 and 24 h). Mares were bred with fresh …

Bone Quality In Ckd Patients: Current Concepts And Future Directions – Part I, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures …

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …

Insects Provide Unique Systems To Investigate How Early-Life Experience Alters The Brain And Behavior, Rebecca R. Westwick, Clare C. Rittschof

Entomology Faculty Publications

Early-life experiences have strong and long-lasting consequences for behavior in a surprising diversity of animals. Determining which environmental inputs cause behavioral change, how this information becomes neurobiologically encoded, and the functional consequences of these changes remain fundamental puzzles relevant to diverse fields from evolutionary biology to the health sciences. Here we explore how insects provide unique opportunities for comparative study of developmental behavioral plasticity. Insects have sophisticated behavior and cognitive abilities, and they are frequently studied in their natural environments, which provides an ecological and adaptive perspective that is often more limited in lab-based vertebrate models. A range of cues, …

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

Improvisation As A Teaching Tool For Improving Oral Communication Skills In Premedical And Pre-Biomedical Graduate Students, Marianne Phelps, Catrina White, Lin Xiang, Hollie I. Swanson

Theatre and Dance Faculty Publications

Objective:

To evaluate the relationship between training in theatre improvisation and empathy, communication, and other professional skills.

Methods:

Undergraduate and graduate students who were participants of a 10-week summer undergraduate research program engaged in theatre improvisation techniques during a 3-hour workshop. In Study #1, a de-identified, self-report questionnaire (known as the Empathy Quotient) was administered prior to and following the workshop. Paired sample 2-tailed t-tests were performed to evaluate pre- and post-test scores. To identify additional benefits of engaging in theatre improvisation techniques, Study #2 was performed. Here, a survey was administered to the participants following their completion of …

Case Report: The Complexities Of Managing Medications And The Importance Of Deprescribing Anticholinergics In Older Adults, Taylor Elliott, Lynne Eckmann, Daniela C. Moga

Pharmacy Practice and Science Faculty Publications

Potentially inappropriate anticholinergic medications (including over-the-counter products), polypharmacy, and the existence of communication barriers among members of the interprofessional team frequently contribute to clinical complexity in older adults. We present the case of a frail 86-year old female from the perspective of a community pharmacist managing outpatient medications and transitions of care. CD’s past medical history is significant for dementia, multiple falls, recurrent urinary tract infections, depression, cardiac arrhythmia, macular degeneration, chronic pain, depression, and cerebrovascular disease.

Antibiotic Prescription Practices And Opinions Regarding Antimicrobial Resistance Among Veterinarians In Kentucky, Usa, Agricola Odoi, Ronita Samuels, Craig N. Carter, Jackie Smith

Veterinary Diagnostic Laboratory Faculty Publications

Background
Inappropriate antimicrobial use (AMU) is a global concern. Opinions of veterinarians regarding AMU and its role in the development of antimicrobial resistance (AMR) may influence their prescription practices. It is important to understand these opinions, prescription practices and their potential impact on the development of AMR in order to guide efforts to curb the problem. Therefore, the objective of this study was to investigate the antimicrobial prescription practices and opinions of veterinarians in Kentucky regarding AMU and AMR.

Methods
This cross-sectional study used a 30-question survey questionnaire administered to veterinarians who were members of the Kentucky Veterinary Medical Association. …

Functional Activation Of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis, Natalie N. Nawarawong, Chelsea G. Nickell, Deann M. Hopkins, James R. Pauly, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were …

Gait And Balance Changes With Investigational Peripheral Nerve Cell Therapy During Deep Brain Stimulation In People With Parkinson’S Disease, Geetanjali Gera, Zain Guduru, Tritia R. Yamasaki, Julie A. Gurwell, Monica Chau, Anna Krotinger, Frederick A. Schmitt, John T. Slevin, Greg A. Gerhardt, Craig G. Van Horne, Jorge E. Quintero

Physical Therapy Faculty Publications

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the …

Vitamin D Promotes Skeletal Muscle Regeneration And Mitochondrial Health, Christine M. Latham, Camille R. Brightwell, Alexander R. Keeble, Brooke D. Munson, Nicholas T. Thomas, Alyaa M. Zagzoog, Christopher S. Fry, Jean L. Fry

Athletic Training and Clinical Nutrition Faculty Publications

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated …

Keap1 Is Required For Artesunate Anticancer Activity In Non-Small-Cell Lung Cancer, Kristen S. Hill, Anthony Mcdowell Jr., J. Robert Mccorkle, Erin Schuler, Sally R. Ellingson, Rina Plattner, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

Artesunate is the most common treatment for malaria throughout the world. Artesunate has anticancer activity likely through the induction of reactive oxygen species, the same mechanism of action utilized in Plasmodium falciparum infections. Components of the kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which regulates cellular response to oxidative stress, are mutated in approximately 30% of non-small-cell lung cancers (NSCLC); therefore, we tested the hypothesis that KEAP1 is required for artesunate sensitivity in NSCLC. Dose response assays identified A549 cells, which have a G333C-inactivating mutation in KEAP1, as resistant to artesunate, with an IC50 of …

Method For Designing Compounds And Compositions Useful For Targeting High Stoichiometric Complexes To Treat Conditions, Including Treatment Of Viruses, Bacteria, And Cancers Having Acquired Drug Resistance, Peixuan Guo, Dan Shu

Pharmaceutical Sciences Faculty Patents

A method is described for the identification o f multi-subunit biocomplex drug targets. The method includes identifying a target that performs a biological function, wherein the target comprises one or more subunits, wherein a minimum number of the one or more subunits is inactivated to inhibit the biological function. The method includes selecting a drug that binds specifically to each subunit of the one or more subunits with a target probability. The method describes a relationship between inhibition efficiency of the drug and total number of the one or more subunits using a binomial distribution, wherein the inhibition efficiency comprises …

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10⁻⁷²), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 …