Medical Specialties Commons^™

Dysregulation Of Systemic Immunity In Aging And Dementia, Jenny Lutshumba, Barbara S. Nikolajczyk, Adam D. Bachstetter

Pharmacology and Nutritional Sciences Faculty Publications

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks …

Analysis Of High-Risk Pedigrees Identifies 12 Candidate Variants For Alzheimer's Disease, Craig C. Teerlink, Justin B. Miller, Elizabeth L. Vance, Lyndsay A. Staley, Jeffrey Stevens, Justina P. Tavana, Matthew E. Cloward, Madeline L. Page, Louisa Dayton, Alzheimer's Disease Genetics Consortium, Lisa A. Cannon-Albright, John S. K. Kauwe

Institute for Biomedical Informatics Faculty Publications

INTRODUCTION: Analysis of sequence data in high-risk pedigrees is a powerful approach to detect rare predisposition variants.

METHODS: Rare, shared candidate predisposition variants were identified from exome sequencing 19 Alzheimer's disease (AD)-affected cousin pairs selected from high-risk pedigrees. Variants were further prioritized by risk association in various external datasets. Candidate variants emerging from these analyses were tested for co-segregation to additional affected relatives of the original sequenced pedigree members.

RESULTS: AD-affected high-risk cousin pairs contained 564 shared rare variants. Eleven variants spanning 10 genes were prioritized in external datasets: rs201665195 (ABCA7), and rs28933981 (TTR) were previously …

Extrapulmonary Tuberculosis: A Case Report Involving The Spine And Soft Tissues, Aden Gunnar Miller, Paul J. Spicer

Radiology Faculty Publications

Tuberculosis (TB) is a major health concern worldwide, and its incidence is increasing in developed countries, especially among immigrant populations. Extrapulmonary TB with musculoskeletal involvement is often a difficult and delayed diagnosis, as the disease can mimic metastases or infection. We present a case of extrapulmonary TB affecting the spine and soft tissues of a Vietnamese-born patient living in the United States. We discuss the imaging findings associated with extrapulmonary TB of the spine. Familiarity with key imaging features of disease can lead to early suspicion and detection of the disease as well as timely treatment.

Q134r: Small Chemical Compound With Nfat Inhibitory Properties Improves Behavioral Performance And Synapse Function In Mouse Models Of Amyloid Pathology, Pradoldej Sompol, Jenna L. Gollihue, Susan D. Kraner, Irina A. Artiushin, Ryan A. Cloyd, Emad Chishti, Shon A. Koren, Grant K. Nation, Jose F. Abisambra, Orsolya Huzian, Lajos I. Nagy, Miklos Santha, Laszlo Hackler Jr., Laszlo G. Puskas, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. …

Acute-Onset Central Serous Retinopathy After Immunization With Covid-19 Mrna Vaccine, Nicholas Fowler, Noe R. Mendez Martinez, Bernardo Velazquez Pallares, Ramiro S. Maldonado

Ophthalmology and Visual Science Faculty Publications

Purpose
We report the case of a 33-year-old male who presented with unilateral central serous retinopathy three days after the injection of a COVID-19 vaccine.

Observations
A 33-year-old healthy Hispanic male referred to the ophthalmology service due to blurry vision and metamorphopsia in the right eye without any flashes, floaters, eye redness or pain. The patient reported that 69 hours prior to presentation he received the first dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. He denied any past ocular history or pertinent medical history. He does not take any medicines and denies stressful factors in his life. The clinical …

Aerosolized Surfactant For Preterm Infants With Respiratory Distress Syndrome, Mandy Brasher, Thomas M. Raffay, M. Douglas Cunningham, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

Currently, the administration of surfactant to preterm infants with respiratory distress syndrome (RDS) mainly relies on intratracheal instillation; however, there is increasing evidence of aerosolized surfactant being an effective non-invasive strategy. We present a historical narrative spanning sixty years of development of aerosolization systems. We also offer an overview of the pertinent mechanisms needed to create and manage the ideal aerosolization system, with a focus on delivery, distribution, deposition, and dispersion in the context of the human lung. More studies are needed to optimize treatment with aerosolized surfactants, including determination of ideal dosages, nebulizer types, non-invasive interfaces, and breath synchronization. …

Limitations In American Adults’ Awareness Of And Beliefs About Alcohol As A Risk Factor For Cancer, Marc T. Kiviniemi, Heather Orom, Jennifer L. Hay, Erika A. Waters

Health, Behavior & Society Faculty Publications

Alcohol is a carcinogen. Recommendations to reduce alcohol use to lower cancer risk are increasingly common. However, neither the beliefs of US adults about alcohol consumption and cancer risk, nor factors influencing those beliefs, are well understood. We used data from the 2019 Health Information National Trends Survey (analysis N = 4,470) to examine beliefs about whether drinking too much alcohol increases cancer risk. We compared those beliefs to beliefs for three other health problems, and examined whether believing alcohol is a cancer risk factor was related to demographics, risk perceptions, other beliefs about the nature of cancer, and alcohol …

Cd151 Drives Cancer Progression Depending On Integrin Α3Β1 Through Egfr Signaling In Non-Small Cell Lung Cancer, Jianjie Zhu, Tingting Cai, Jieqi Zhou, Wenwen Du, Yuanyuan Zeng, Ting Liu, Yulong Fu, Yue Li, Qian Qian, Xiuwei H. Yang, Qinglin Li, Jian-An Huang, Zeyi Liu

Pharmacology and Nutritional Sciences Faculty Publications

Background
Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion.

Methods
First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified …

Opportunities To Improve Symptom Control With Somatostatin Congeners In Gep-Nets: A Review Of Key Issues, Lowell B. Anthony, Thomas M. O'Dorisio

Internal Medicine Faculty Publications

Octreotide acetate (octreotide) is the most prescribed and most studied somatostatin congener, or analog, for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and carcinoid syndrome, the latter of which may be characterized by debilitating diarrhea and flushing. Approved in the U.S. more than 30 years ago, octreotide is widely used to control the symptoms of carcinoid syndrome and has been shown to demonstrate antiproliferative activity. The two formulations available in the U.S. include a subcutaneous immediate-release (IR) injection introduced in 1989 and a long-acting repeatable (LAR) intramuscular injection approved in 1999. Lanreotide depot (lanreotide), a more recent somatostatin congener, has been available in …

Prevalence Of Tp-53/Rb-1 Co-Mutation In Large Cell Neuroendocrine Carcinoma, Hoda Saghaeiannejad Esfahani, Cory M. Vela, Aman Chauhan

Internal Medicine Faculty Publications

Introduction: Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive high-grade neuroendocrine neoplasm, which can arise from anywhere in the body. Due to its rarity there is a lacuna in our understanding of LCNEC’s molecular biology. In 2016, Rekhtman and colleagues presented one of the largest molecular sequencing series of pulmonary LCNEC. They differentiated genomic profiles of LCNEC into two major subsets: small cell lung cancer (SCLC)-like, characterized by TP53 + RB1 co-mutation/loss, and non-small cell lung cancer (NSCLC)-like, characterized by the lack of co-altered TP53 + RB1. This finding is of significance because at present LCNEC patients …

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 …

Evaluation Of Multi-Level Barriers And Facilitators In A Large Diabetic Retinopathy Screening Program In Federally Qualified Health Centers: A Qualitative Study, Ana Bastos De Carvalho, S. Lee Ware, Tamara Belcher, Franceska Mehmeti, Eric B. Higgins, Robert Sprang, Cody Williams, Jamie L. Studts, Christina R. Studts

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Recommended annual diabetic retinopathy (DR) screening for people with diabetes has low rates in the USA, especially in underserved populations. Telemedicine DR screening (TDRS) in primary care clinics could expand access and increase adherence. Despite this potential, studies have observed high variability in TDRS rates among clinics and over time, highlighting the need for implementation supports. Previous studies of determinants of TDRS focus on patients' perspectives, with few studies targeting upstream multi-level barriers and facilitators. Addressing this gap, this qualitative study aimed to identify and evaluate multi-level perceived determinants of TDRS in Federally Qualified Health Centers (FQHCs), to inform …

Inflammatory Regulation Of Cns Barriers After Traumatic Brain Injury: A Tale Directed By Interleukin-1, Colleen N. Bodnar, James B. Watson, Emma K. Higgins, Ning Quan, Adam D. Bachstetter

Neuroscience Faculty Publications

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during …

Operative Management Of Symptomatic, Metachronous Carotid Body Tumors Involving The Skull Base And Its Neurological Sequelae, Roberto G. Aru, Rony K. Aouad, Justin F. Fraser, Amanda M. Romesberg, Kevin W. Hatton, Sam C. Tyagi

Otolaryngology--Head & Neck Surgery Faculty Publications

A 44-year-old morbidly obese woman with a history of right carotid body tumor (CBT) resection presented with a symptomatic, nonfunctional, left Shamblin-III CBT. Abutment of the skull base precluded distal internal carotid artery control for arterial reconstruction, favoring parent vessel sacrifice after an asymptomatic provocative test. She underwent CBT resection with anticipated sacrifice of cranial nerves X and XII and the common carotid artery and its branches, developing baroreceptor failure syndrome and sequelae of cranial nerve sacrifice. When facing a symptomatic, metachronous CBT abutting the skull base, upfront operative intervention with adjuvant radiation for residual tumor optimizes curative resection.

Can An Amino Acid Mixture Alleviate Gastrointestinal Symptoms In Neuroendocrine Tumor Patients?, Aman Chauhan, Satya Das, Rachel Miller, Laura Luque, Samuel N. Cheuvront, James Cloud, Zach Tarter, Fariha Siddiqui, Robert A. Ramirez, Lowell B. Anthony

Internal Medicine Faculty Publications

Background: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models.

Methods: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval.

Results: Ninety-eight NET patients who …

Pi3k/Mtor Dual Inhibitor Pf-04691502 Is A Schedule-Dependent Radiosensitizer For Gastroenteropancreatic Neuroendocrine Tumors, Zeta Chow, Jeremy Johnson, Aman Chauhan, Tadahide Izumi, Michael Cavnar, Heidi L. Weiss, Courtney M. Townsend Jr., Lowell B. Anthony, Carrigan Wasilchenko, Matthew L. Melton, Jörg Schrader, B. Mark Evers, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up …

Opioid And/Or Psychotropic Use Increases Intraprocedural Sedation Drug Requirements, Sreeja Sanampudi, Ravi Jayavarapu, Trae C. Brooks, Driss Raissi

Radiology Faculty Publications

Objectives Acute pain management in opioid users can be challenging in the perioperative period. This study focuses on whether use of opioids increases sedation medication requirements in patients undergoing port placement under moderate sedation.

Materials and Methods A retrospective review was performed on all patients undergoing port placement between June 1, 2017, and June 30, 2019. Exclusion criteria included receiving general anesthesia, no sedation, and errors in data entry. Data collection included demographics, use of opioids, benzodiazepines, antidepressants, tobacco, alcohol, and sedation data.

Results Opioid, benzodiazepine, and selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) use was significantly associated with …

A Metabolomic Endotype Of Bioenergetic Dysfunction Predicts Mortality In Critically Ill Patients With Acute Respiratory Failure, Raymond J. Langley, Marie E. Migaud, Lori Flores, J. Will Thompson, Elizabeth A. Kean, Murphy M. Mostellar, Matthew Mowry, Patrick Luckett, Lina D. Purcell, James Lovato, Sheetal Gandotra, Ryan Benton, D. Clark Files, Kevin S. Harrod, Mark N. Gillespie, Peter E. Morris

Internal Medicine Faculty Publications

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. …

A Highly Predictive Microrna Panel For Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin Xie, David W. Fardo, Kevin W. Hatton

Sanders-Brown Center on Aging Faculty Publications

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV …

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells …

Myocarditis Concurrent With Sweet Syndrome: A Presentation Of Acute Myeloid Leukemia, Christopher G. Burkeen, David Pottinger, Chaitanya Iragavarapu, Reshma Ramlal, Gerhard C. Hildebrandt

Markey Cancer Center Faculty Publications

Acute myeloid leukemia (AML) is the most common acute leukemia in American adults and portends a poor prognosis if untreated. Commonly, AML presents with symptoms related to concurrent leukopenia, anemia, or thrombocytopenia; however, due to its ability to affect many organ systems in the body, AML can have a highly varied clinical presentation. One such presentation is myocarditis, which is a rarely reported manifestation of AML. Myocarditis can have a varied clinical picture and often requires exclusion of other causes of cardiac dysfunction. Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is another presentation of AML; however, it is …

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …

Cardiovascular Complications Of Systemic Lupus Erythematosus: Impact Of Risk Factors And Therapeutic Efficacy--A Tertiary Centre Experience In An Appalachian State, Elise Danielle Mcveigh, Amna Batool, Arnold J. Stromberg, Ahmed K. Abdel-Latif, Nayef Mohammed Kazzaz

Statistics Faculty Publications

OBJECTIVES: Cardiovascular complications became a notable cause of morbidity and mortality in patients with lupus as therapeutic advancements became more efficient at managing other complications. The Appalachian community in Kentucky has a higher prevalence of traditional cardiovascular risk factors, predisposing them to cardiovascular events. Namely, the mean body mass index of the members of the Kentucky Appalachian community was reported at 33 kg/m² and 94.3% of male members of this community use tobacco. We sought to identify risk factors that predispose patients with lupus to cardiovascular morbidities and examine the effect of immunomodulatory drugs.

METHODS: We identified 20 UKHS …

Loss Of Obstetric Services In Rural Appalachia: A Qualitative Study Of Community Perceptions, Caroline R. Efird, David Dry, Rachel F. Seidman

Journal of Appalachian Health

Background: As rural hospitals across the United States increasingly downsize or close, the availability of inpatient obstetric services continues to decline in rural areas. In rural Appalachia, the termination of obstetric services threatens to exacerbate the existing risk of adverse birth outcomes for women and infants, yet less is known about how the cessation of these services affects the broader community.

Purpose: The purpose of this paper is to explain how the loss of local obstetric services affects perceptions of healthcare among multi-generational residents of a remote, rural Appalachian community in western North Carolina.

Methods: An interdisciplinary team of researchers …

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 …

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.

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, …

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 …