Medicine and Health Sciences Commons^™

Moral Status And The Oversight Of Research Involving Chimeric Animals, Patricia Marshall, Kaitlynn P. Craig

Faculty Scholarship

The use of nonhuman animals in research has long been a source of bioethical and scientific debate. We consider the oversight and use of nonhuman animals in chimeric research. We conducted interviews with twelve members of embryonic stem cell research oversight committees, nine members of institutional animal care and use committees, and fourteen scientists involved in human–nonhuman-animal chimeric research in different areas of the United States. Interviews addressed animal welfare and conceptual issues associated with moral status and humanization of nonhuman animals that contain human cells. Our findings suggest that concepts of enhanced moral status and consciousness are not very …

Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan

Faculty Scholarship

Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including …

Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan

Faculty Scholarship

Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases …

Survey Tools For Measuring Research Or Evidence‐Based Practice Constructs In Dietetics: A Narrative Review, Rosa K. Hand

Faculty Scholarship

Background: Exact quantification of research conducted by dietitians and tracking the effectiveness of interventions or training programs to increase either evidence-based practice (EBP) or research behaviours have been hampered by the variety of tools used to measure these constructs. Methods: In this narrative review, we identified and classified the various tools previously used to measure constructs related to research and/or EBP in the dietetics profession, and to summarise estimates of the constructs measured. Results: We identified and classified 15 scored tools that had been used at least once in the dietetics profession and extracted tool parameter estimates from 22 resulting …

The Detection Of Periodic Reemergence Events Of Sars-Cov-2 Delta Strain In Communities Dominated By Omicron, Claire E. Westcott, Kevin J. Sokoloski, Eric C. Rouchka, Julia H. Chariker, Rochelle H. Holm, Ray A. Yeager, Joseph B. Moore Iv, Erin M. Elliott, Daymond Talley, Aruni Bhatnagar

Faculty Scholarship

Despite entering an endemic phase, SARS-CoV-2 remains a significant burden to public health across the global community. Wastewater sampling has consistently proven utility to understanding SARS-CoV-2 prevalence trends and genetic variation as it represents a less biased assessment of the corresponding communities. Here, we report that ongoing monitoring of SARS-CoV-2 genetic variation in samples obtained from the wastewatersheds of the city of Louisville in Jefferson county Kentucky has revealed the periodic reemergence of the Delta strain in the presence of the presumed dominant Omicron strain. Unlike previous SARS-CoV-2 waves/emergence events, the Delta reemergence events were geographically restricted in the community …

The Impact Of Obesity And Adipokines On Breast And Gynecologic Malignancies, Surabhi Tewari, Roberto Vargas, Ofer Reizes

Faculty Scholarship

The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer-related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat-secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we …

Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta

Faculty Scholarship

Sickle cell disease (SCD) is an inherited blood disorder that affects ~100,000 Americans (1, 2). In SCD, red blood cells (RBC) containing aberrant sickle hemoglobin (HgbS) become sickle-shaped at low oxygen tension and stick together leading to obstructed blood flow. The resulting decrease in tissue oxygenation causes chronic complications such as vasculo-occlusive pain crises among others that require frequent hospitalizations (3). Chronic RBC transfusions play a prominent role in the treatment of this disease by improving oxygenation through addition of normal RBC and dilution of RBC containing HgbS (4, 5). However, the major disadvantage of management with simple transfusion is …

The Effects Of Cannabidiol On Aqueous Humor Outflow And Trabecular Meshwork Cell Signaling, Alyssa S. Aebersold, Zhao-Hui Song

Faculty Scholarship

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin …

Association Of Hypomagnesemia And Liver Injury, Role Of Gut-Barrier Dysfunction And Inflammation: Efficacy Of Abstinence, And 2-Week Medical Management In Alcohol Use Disorder Patients., Evan J. Winrich, Khushboo S. Gala, Abhas Rajhans, Christian D. Rios-Perez, Amor J. Royer, Zarlakhta Zamani, Ranganathan Parthasarathy, Luis S. Marsano-Obando, Ashutosh J. Barve, Melanie L. Schwandt, Vatsalya Vatsalya

Faculty Scholarship

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

A Novel Approach To Assessment Of Us Pediatric Trauma System Development., Mary E. Fallat, Colin Traeger, Sophie Humphrey, Lindsey Gumer, Kahir Jawad, Elissa Butler, Frederick B. Rogers, Frederick P. Rivara, Amelia T. Collings

Faculty Scholarship

Importance Mature trauma systems are critical in building and maintaining national, state, and local resilience against all-hazard disasters. Currently, pediatric state trauma system plans are not standardized and thus are without concrete measures of potential effectiveness.

Objective To develop objective measures of pediatric trauma system capability at the state level, hypothesizing significant variation in capabilities between states, and to provide a contemporary report on the status of national pediatric trauma system planning and development.

Design, Setting, and Participants A national survey was deployed in 2018 to perform a gap analysis of state pediatric trauma system capabilities. Four officials from each …

Coexistence Of Cutaneous Squamous Cell Carcinoma And Basal Cell Carcinoma In A Renal Transplant Recipient: A Case Report., Diana Voloshyna, Tanveer Ahamad Shaik, Sunita Shrestha, Ajmat Ansari, Faraz Saleem, Muhammad Abu Zar Ghaffari

Faculty Scholarship

In solid organ transplant patients, non-melanoma skin cancer remains a leading cause of mortality. The most common skin malignancies in solid organ transplant patients are squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In organ transplant patients, SCC is 100 times more prevalent, and BCC is 10 times more prevalent than in the general population. Many risk factors for developing such malignancies are equivalent to those in the general population. However, in the transplant population, such cancers occur at an earlier age, act more aggressively, and often appear at multiple locations. Thus, assiduousness on the patient's part and healthcare …

Retroperitoneal Ancient Neurilemmoma: A Nervous Rarity., Vaidehi Mendpara, Sweta Sahu, Devarsh N. Shaw, Subhangi Parmar, Tanveer Ahamad Shaik, Swastika Sadhai, Mukesh Pancholi

Faculty Scholarship

Neurilemmomas are tumors of neural origin that comprise Schwann cell proliferation in a characteristic pattern. They are benign in nature. Ancient neurilemmomas are usually longstanding growths that exhibit degenerative features that could be mistaken for malignancy. We report a case of ancient neurilemmoma in a 70-year-old male patient in the retroperitoneal area. Retroperitoneal schwannomas are extremely uncommon along with ancient neurilemmoma features making it worth reporting

Quantifying The Relationship Between Sub-Population Wastewater Samples And Community-Wide Sars-Cov-2 Seroprevalence, Ted Smith, Rochelle H. Holm, Rachel J. Keith, Alok R. Amraotkar, Chance R. Alvarado, Krzysztof Banecki, Boseung Choi, Ian Santisteban, Adrienne M. Bushau-Sprinkle, Kathleen T. Kitterman, Joshua Fuqua, Krystal T. Hamorsky, Kenneth E. Palmer, J. Michael Brick, Aruni Bhatnagar, Grzegorz A. Rempala

Faculty Scholarship

Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies in 3717 participants and obtained weekly samples of community wastewater for SARS-CoV-2 concentrations in Jefferson County, KY (USA) from August 2020 to February 2021. Using an expanded Susceptible-Infected-Recovered model, the longitudinal estimates of the disease prevalence were obtained and compared with the wastewater concentrations using regression analysis. The model analysis …

“Flipped” Clinical Rotations: A Novel Approach, Wei Xiong, Simran Singh, Amy Wilson-Delfosse, Robert Jones, Craig Nielsen, Carol Chalkley, Lia Logio

Faculty Scholarship

Background: Near the beginning of the COVID-19 pandemic in the United States, medical students were pulled out of all in-person patient care activities. This resulted in massive disruption to the required clinical rotations (clerkships), necessitating creative curricular solutions to ensure continued education for medical students. Approach: In response to the lockout, our school adopted a “flipped” clinical rotations model that assigned students to remote learning activities prior to in-person patient care activities. This approach allowed students to continue their clinical education virtually with a focus on knowledge for practice while awaiting return to the shortened in-person portions of their rotation. …

Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan

Faculty Scholarship

Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up …

Update On The Management Of Vitamins And Minerals In Cystic Fibrosis, Senthilkumar Sankararaman

Faculty Scholarship

Advancements in respiratory and nutrition management have significantly improved the survival of patients with cystic fibrosis (CF). With the availability of several nutrition interventions such as oral/enteral nutrition supplements, enteric-coated pancreatic enzymes, and water-miscible CF-specific vitamin supplements, frank vitamin deficiencies—with the exception of vitamin D—are rarely encountered in current clinical practice. Whereas they were previously considered as micronutrients, our current understanding of fat-soluble vitamins and minerals as antioxidants, immunomodulators, and disease biomarkers has been evolving. The impact of highly effective modulators on the micronutrient status of patients with CF remains elusive. This narrative review focuses on the updates on the …

Temporal And Sex-Linked Protein Expression Dynamics In A Familial Model Of Alzheimer's Disease, Filipa Blasco Tavares Pereira Lopes, Daniela M. Schlatzer, Rihua Wang, Xiaolin Li, Emily Feng, Mehmet Koyutürk, Xin Qi, Mark R. Chance

Faculty Scholarship

Mouse models of Alzheimer's disease (AD) show progression through stages reflective of human pathology. Proteomics identification of temporal and sex-linked factors driving AD-related pathways can be used to dissect initiating and propagating events of AD stages to develop biomarkers or design interventions. In the present study, we conducted label-free proteome measurements of mouse hippocampus tissue with variables of time (3, 6, and 9 months), genetic background (5XFAD versus WT), and sex (equal males and females). These time points are associated with well-defined phenotypes with respect to the following: Aβ42 plaque deposition, memory deficits, and neuronal loss, allowing correlation of proteome-based …

Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …

Increased Cytokine Gene Expression And Cognition Risk Associated With Androgen Deprivation Therapy, Shiv Verma, Prem Prakash Kushwaha, Eswar Shankar, Lee E. Ponsky, Sanjay Gupta

Faculty Scholarship

Background: Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. Methods: Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge …

Palliative Stenting Of The Venous Duct In A Premature Neonate With Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Connection, John S. Lozier, Martin L. Bocks

Faculty Scholarship

In infracardiac, infradiaphragmatic total anomalous pulmonary venous connection, all four pulmonary veins connect to a descending vertical vein that usually drains to the portal vein or one of its tributaries. Obstruction is common, and definitive treatment is surgical repair. We present a case of late-diagnosed infradiaphragmatic total anomalous pulmonary venous connection in a premature neonate who was too high risk for surgery and underwent palliative stenting of the venous duct. We demonstrate the feasibility of a transhepatic approach when umbilical access is no longer available.

Health Concerns Of Kentucky's Library Workforce During The Early Covid-19 Pandemic., Anita R. Hall, Brandi Duggins

Faculty Scholarship

Although research early in the pandemic primarily emphasized libraries’ pandemic response and service to patrons, more interest has developed regarding library workers and their experiences. This study seeks to understand the impacts library workers experienced from the beginning of institutions’ initial pandemic response through the end of 2020. This article focuses on a subset of the data related to the health concerns and impacts Kentucky library workers experienced during distinct phases of the early pandemic. Responses to this survey indicate that workers required to be onsite were impacted more frequently with COVID-related health concerns while all library workers experienced significant …

Examining How Congruence In And Satisfaction With Dyadic Care Type Appraisal Contribute To Quality Of Life In Heart Failure Care Dyads, Elliane Irani, Seunghee Margevicius

Faculty Scholarship

AIMS: Given the complexity of heart failure (HF) management, persons with HF and their informal caregivers often engage in dyadic illness management. It is unknown how congruent appraisal of dyadic HF care type is associated with dyadic health. Our aim was to examine how congruence in and satisfaction with appraisal of dyadic HF care type contribute to quality of life (QOL) for dyads. METHODS AND RESULTS: This is a secondary analysis of cross-sectional data on 275 HF care dyads (patients 45.1% female, caregivers 70.5% female). Congruent appraisal and satisfaction were assessed using the Dyadic Symptom Management Type instrument. Quality of …

Respiratory Morbidity And Neurodevelopmental Outcomes In Infants Born Preterm: A Complex Web, Anna Maria Hibbs

Faculty Scholarship

This commentary is on the original article by Yu et al. on pages 1246–1253 of this issue.

Evaluation Of Periodontal Status And Cytokine Levels In Saliva And Gingival Crevicular Fluid Of Patients With Inflammatory Bowel Diseases, Andre Paes Batista Da Silva

Faculty Scholarship

Background: Periodontal diseases and inflammatory bowel diseases (IBD, ulcerative colitis [UC] and Crohn disease [CD]) have been reported to present with increased salivary and gingival crevicular fluid (GCF) concentrations of cytokines. The aim of this study was to evaluate the salivary and GCF levels of TNF-α, IL-1β, IL-10, and IL-17A and their associations with the periodontal statuses of UC, CD, and non-IBD patients, and to analyze the interrelationships among these cytokines, IBD conditions, and periodontal diseases. Methods: This cross-sectional study was performed with a total of 131 patients (62 women and 69 men, mean age 42.96±13.02 years). Patients were divided …

Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse

Faculty Scholarship

U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

Obesity Accelerates Acute Promyelocytic Leukemia In Mice And Reduces Sex Differences In Latency And Penetrance, John W. R. Kincaid, Gretchen Weiss, Anne E. Hill-Baskin, Heidi M. Schmidt, Ovwoioise Omoijuanfo, Cheryl L. Thompson, Rose C. Beck, Nathan A. Berger

Faculty Scholarship

Objective: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). Methods: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. …

Extrusion: A New Method For Rapid Formulation Of High-Yield, Monodisperse Nanobubbles, Claire Counil, Eric Abenojar, Reshani Perera, Agata A. Exner

Faculty Scholarship

Shell-stabilized gas microbubbles (MB) and nanobubbles (NB) are frequently used for biomedical ultrasound imaging and therapeutic applications. While it is widely recognized that monodisperse bubbles can be more effective in these applications, the efficient formulation of uniform bubbles at high concentrations is difficult to achieve. Here, it is demonstrated that a standard mini-extruder setup, commonly used to make vesicles or liposomes, can be used to quickly and efficiently generate monodisperse NBs with high yield. In this highly reproducible technique, the NBs obtained have an average diameter of 0.16 ± 0.05 µm and concentration of 6.2 ± 1.8 × 1010 NBs …

Urate-Lowering Therapy For Patients With Gout On Hemodialysis, Reem Alkilany, Douglas Einstadter, Maria Antonelli

Faculty Scholarship

Objective: Gout is the most common form of inflammatory arthritis and is caused by deposition of monosodium urate crystals resulting from a high burden of uric acid (UA). High UA burden also has been associated with increased morbidity and mortality in the general population and progression to chronic kidney disease. In persons with gout and end-stage renal disease (ESRD), prior studies suggest that UA levels decrease after initiation of hemodialysis (HD). We evaluated UA level and the use of urate-lowering therapies (ULTs) in patients with gout and ESRD on HD. Methods: We performed a retrospective review of patients with gout …

The Time-Varying Cardiovascular Benefits Of Glucagon-Like Peptide-1 Receptor Agonist Therapy In Patients With Type 2 Diabetes Mellitus: Evidence From Large Multinational Trials, Salil V. Deo, Yakov Elgudin

Faculty Scholarship

Aims: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. Material and Methods: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran's Q statistic. …