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Full-Text Articles in Medical Specialties

Palbociclib Treatment Alters Nucleotide Biosynthesis And Glutamine Dependency In A549 Cells, Lindsey R. Conroy, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Shesh N. Rai, Brian F. Clem Jul 2020

Palbociclib Treatment Alters Nucleotide Biosynthesis And Glutamine Dependency In A549 Cells, Lindsey R. Conroy, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Shesh N. Rai, Brian F. Clem

Neuroscience Faculty Publications

Background

Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown.

Methods

In …


Thrower's Exostosis Of The Shoulder: A Systematic Review With A Novel Classification, Michael T. Freehill, Sandeep Mannava, Laurence D. Higgins, Alexandre Lädermann, Austin V. Stone Jul 2020

Thrower's Exostosis Of The Shoulder: A Systematic Review With A Novel Classification, Michael T. Freehill, Sandeep Mannava, Laurence D. Higgins, Alexandre Lädermann, Austin V. Stone

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: A variety of thrower's exostoses are grouped under the term Bennett lesion, which makes understanding diagnosis and treatment difficult.

Purpose: To identify all types of reported thrower's and overhead athlete's exostoses and categorize them into a classification system to allow a morphology-based classification.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review of all articles pertaining to Bennett lesions and thrower's exostosis was performed. The classification and treatments were evaluated to describe the types, proposed causes, diagnosis, and treatment options.

Results: A total of 27 studies were included in the systematic review. The anatomic locations …


Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She Jun 2020

Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis …


Evolving Role For Pharmacotherapy In Nafld/Nash, Suzanna L. Attia, Samir Softic, Marialena Mouzaki Jun 2020

Evolving Role For Pharmacotherapy In Nafld/Nash, Suzanna L. Attia, Samir Softic, Marialena Mouzaki

Pediatrics Faculty Publications

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no US Food and Drug Administration (FDA) approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance, and lipid handling within the liver. Three drugs have gone on to phase III trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise …


Resolving Metabolic Heterogeneity In Experimental Models Of The Tumor Microenvironment From A Stable Isotope Resolved Metabolomics Perspective, Teresa W-M Fan, Richard M. Higashi, Yelena Chernayavskaya, Andrew N. Lane Jun 2020

Resolving Metabolic Heterogeneity In Experimental Models Of The Tumor Microenvironment From A Stable Isotope Resolved Metabolomics Perspective, Teresa W-M Fan, Richard M. Higashi, Yelena Chernayavskaya, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies of TME. As human subjects and in vivo model systems are complex and difficult to manipulate, simpler 3D model systems that are compatible with flexible experimental control are necessary for studying metabolic regulation in TME. Stable Isotope Resolved Metabolomics (SIRM) is a valuable tool for tracing metabolic networks in complex systems, but at present does not directly …


Risk And Protective Factors Of Dementia Among Adults With Post-Traumatic Stress Disorder: A Systematic Review Protocol, Karen A. Lawrence, Theresia M. Pachner, Molly M. Long, Stephanie Henderson, Donna L. Schuman, Brenda L. Plassman Jun 2020

Risk And Protective Factors Of Dementia Among Adults With Post-Traumatic Stress Disorder: A Systematic Review Protocol, Karen A. Lawrence, Theresia M. Pachner, Molly M. Long, Stephanie Henderson, Donna L. Schuman, Brenda L. Plassman

Social Work Faculty Publications

INTRODUCTION: Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia. Individual epidemiological studies have controlled for several confounders of the relationship between PTSD and increased dementia risk, yet particular risk factors underlying this relationship have not been determined. This systematic review protocol aims to identify risk and protective factors of dementia among adults with PTSD.

METHODS AND ANALYSIS: We will conduct an electronic search of the databases: PubMed, CINAHL, PsychINFO, The Cochrane Library, Scopus and ProQuest Dissertation and Theses Global. After screening the studies, quantitative synthesis will be performed, if possible. Otherwise, a narrative synthesis will be …


Endoluminal Graft System And Method Of Implanting The Same, David J. Minion Jun 2020

Endoluminal Graft System And Method Of Implanting The Same, David J. Minion

Surgery Faculty Patents

An endoluminal graft system comprising an endoluminal graft including a framework and a flexible fabric surrounding the framework, a deflection means configured for placement through an opening to a branching vessel, and a delivery catheter configured to position the endoluminal graft within a primary vessel. A method of implanting the endoluminal graft includes positioning the endoluminal graft within a primary vessel with a leading edge of the endoluminal graft adjacent to an opening to a branching vessel. A deflecting means is positioned through the opening to the branching vessel adjacent to the leading edge of the endoluminal graft. The endoluminal …


Axillary Artery Pseudoaneurysm Following Percutaneous Transaxillary Access For Impella Device Placement During Percutaneous Coronary Intervention, Anas A. Alharbi, Fahad S. Alqahtani, Peter Farjo, Jason A. Moreland Jun 2020

Axillary Artery Pseudoaneurysm Following Percutaneous Transaxillary Access For Impella Device Placement During Percutaneous Coronary Intervention, Anas A. Alharbi, Fahad S. Alqahtani, Peter Farjo, Jason A. Moreland

Internal Medicine Faculty Publications

Percutaneous transaxillary access is currently considered an acceptable alternative to transfemoral approach for large-bore access, especially in the setting of hostile iliofemoral arteries. Few published reports exist concerning complications of upper extremity access. We describe development of an axillary artery pseudoaneurysm and its management following transaxillary access. (Level of Difficulty: Advanced.)


Postnatal Loss Of The Insulin Receptor In Osteoprogenitor Cells Does Not Impart A Metabolic Phenotype, John L. Fowlkes, R. Clay Bunn, Evangelia Kalaitzoglou, Phil Ray, Iuliana Popescu, Kathryn M. Thrailkill Jun 2020

Postnatal Loss Of The Insulin Receptor In Osteoprogenitor Cells Does Not Impart A Metabolic Phenotype, John L. Fowlkes, R. Clay Bunn, Evangelia Kalaitzoglou, Phil Ray, Iuliana Popescu, Kathryn M. Thrailkill

Barnstable Brown Diabetes Center Faculty Publications

The relationship between osteoblast-specific insulin signaling, osteocalcin activation and gluco-metabolic homeostasis has proven to be complex and potentially inconsistent across animal-model systems and in humans. Moreover, the impact of postnatally acquired, osteoblast-specific insulin deficiency on the pancreas-to-skeleton-to-pancreas circuit has not been studied. To explore this relationship, we created a model of postnatal elimination of insulin signaling in osteoprogenitors. Osteoprogenitor-selective ablation of the insulin receptor was induced after ~10 weeks of age in IRl°x/lox/Osx-Cre+/− genotypic male and female mice (designated postnatal-OIRKO). At ~21 weeks of age, mice were then phenotypically and metabolically characterized. Postnatal-OIRKO mice demonstrated …


A Web-Based, Positive Emotion Skills Intervention For Enhancing Posttreatment Psychological Well-Being In Young Adult Cancer Survivors (Empower): Protocol For A Single-Arm Feasibility Trial, John M. Salsman, Laurie E. Mclouth, Michael Cohn, Janet A. Tooze, Mia Sorkin, Judith T. Moskowitz May 2020

A Web-Based, Positive Emotion Skills Intervention For Enhancing Posttreatment Psychological Well-Being In Young Adult Cancer Survivors (Empower): Protocol For A Single-Arm Feasibility Trial, John M. Salsman, Laurie E. Mclouth, Michael Cohn, Janet A. Tooze, Mia Sorkin, Judith T. Moskowitz

Behavioral Science Faculty Publications

BACKGROUND: Adolescent and young adult cancer survivors (AYAs) experience clinically significant distress and have limited access to supportive care services. Interventions to enhance psychological well-being have improved positive affect and reduced depression in clinical and healthy populations but have not been routinely tested in AYAs.

OBJECTIVE: The aim of this protocol is to (1) test the feasibility and acceptability of a Web-based positive emotion skills intervention for posttreatment AYAs called Enhancing Management of Psychological Outcomes With Emotion Regulation (EMPOWER) and (2) examine proof of concept for reducing psychological distress and enhancing psychological well-being.

METHODS: The intervention development and testing are …


Longitudinal Evaluation Of The Effects Of Illness Perceptions And Beliefs About Cardiac Rehabilitation On Quality Of Life Of Patients With Coronary Artery Disease And Their Caregivers, Patricia Thomson, Neil J. Angus, Federico Andreis, Gordon F. Rushworth, Andrea R. Mohan, Misook L. Chung, Stephen J. Leslie May 2020

Longitudinal Evaluation Of The Effects Of Illness Perceptions And Beliefs About Cardiac Rehabilitation On Quality Of Life Of Patients With Coronary Artery Disease And Their Caregivers, Patricia Thomson, Neil J. Angus, Federico Andreis, Gordon F. Rushworth, Andrea R. Mohan, Misook L. Chung, Stephen J. Leslie

Nursing Faculty Publications

Background

Patients’ negative illness perceptions and beliefs about cardiac rehabilitation (CR) can influence uptake and adherence to CR. Little is known about the interpartner influence of these antecedent variables on quality of life of patients with coronary artery disease (CAD) and their family caregivers. The aims of the study were: 1) to assess differences in illness perceptions, beliefs about CR and quality of life between patients with CAD and their family caregivers upon entry to a CR programme and at 6 months follow-up; and 2) to examine whether patients’ and caregivers’ perceptions of the patient’s illness and beliefs about CR …


Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell May 2020

Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell

Internal Medicine Faculty Publications

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca2+ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was …


Anti-Aggregation Effects Of Phenolic Compounds On Α-Synuclein, Kenjiro Ono, Mayumi Tsuji, Tritia R. Yamasaki, Giulio M. Pasinetti May 2020

Anti-Aggregation Effects Of Phenolic Compounds On Α-Synuclein, Kenjiro Ono, Mayumi Tsuji, Tritia R. Yamasaki, Giulio M. Pasinetti

Neurology Faculty Publications

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson's disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the …


Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu May 2020

Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu

Saha Cardiovascular Research Center Faculty Publications

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR …


Ccl2 Overexpression In The Brain Promotes Glial Activation And Accelerates Tau Pathology In A Mouse Model Of Tauopathy, Aurelie Joly-Amado, Jordan Hunter, Zainuddin Quadri, Frank Zamudio, Patricia V. Rocha-Rangel, Deanna Chan, Anisha Kesarwani, Kevin Nash, Daniel C. Lee, Dave Morgan, Marcia N. Gordon, Maj-Linda B. Selenica May 2020

Ccl2 Overexpression In The Brain Promotes Glial Activation And Accelerates Tau Pathology In A Mouse Model Of Tauopathy, Aurelie Joly-Amado, Jordan Hunter, Zainuddin Quadri, Frank Zamudio, Patricia V. Rocha-Rangel, Deanna Chan, Anisha Kesarwani, Kevin Nash, Daniel C. Lee, Dave Morgan, Marcia N. Gordon, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

Innate immune activation is a major contributor to Alzheimer’s Disease (AD) pathophysiology, although the mechanisms involved are poorly understood. Chemokine C-C motif ligand (CCL) 2 is produced by neurons and glial cells and is upregulated in the AD brain. Transgene expression of CCL2 in mouse models of amyloidosis produces microglia-induced amyloid β oligomerization, a strong indication of the role of these activation pathways in the amyloidogenic processes of AD. We have previously shown that CCL2 polarizes microglia in wild type mice. However, how CCL2 signaling contributes to tau pathogenesis remains unknown. To address this question, CCL2 was delivered via recombinant …


Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen May 2020

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …


Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson May 2020

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …


Using Case-Level Context To Classify Cancer Pathology Reports, Shang Gao, Mohammed Alawad, Noah Schaefferkoetter, Lynne Penberthy, Xiao-Cheng Wu, Eric B. Durbin, Linda Coyle, Arvind Ramanathan, Georgia Tourassi May 2020

Using Case-Level Context To Classify Cancer Pathology Reports, Shang Gao, Mohammed Alawad, Noah Schaefferkoetter, Lynne Penberthy, Xiao-Cheng Wu, Eric B. Durbin, Linda Coyle, Arvind Ramanathan, Georgia Tourassi

Kentucky Cancer Registry Faculty Publications

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence-for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We …


Chagas Disease In The New York City Metropolitan Area, Crystal Zheng, Orlando Quintero, Elizabeth K. Revere, Michael B. Oey, Fabiola Espinoza, Yoram A. Puius, Diana Ramirez-Baron, Carlos R. Salama, Luis F. Hidalgo, Fabiana S Machado, Omar Saeed, Jooyoung Shin, Snehal R. Patel, Christina M. Coyle, Herbert B. Tanowitz May 2020

Chagas Disease In The New York City Metropolitan Area, Crystal Zheng, Orlando Quintero, Elizabeth K. Revere, Michael B. Oey, Fabiola Espinoza, Yoram A. Puius, Diana Ramirez-Baron, Carlos R. Salama, Luis F. Hidalgo, Fabiana S Machado, Omar Saeed, Jooyoung Shin, Snehal R. Patel, Christina M. Coyle, Herbert B. Tanowitz

Internal Medicine Faculty Publications

Background

Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor.

Methods

We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment.

Results

The most common country of origin of our patients …


Ccne1 Amplification As A Predictive Biomarker Of Chemotherapy Resistance In Epithelial Ovarian Cancer, Justin W. Gorski, Frederick R. Ueland, Jill M. Kolesar May 2020

Ccne1 Amplification As A Predictive Biomarker Of Chemotherapy Resistance In Epithelial Ovarian Cancer, Justin W. Gorski, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40-60% of patients achieve complete clinical response to first-line chemotherapy, 25% are inherently platinum-resistant or refractory with a median overall survival of about one year. More than 80% of women afflicted with ovarian cancer will recur. Many attempts have been made to understand the mechanism of platinum and taxane based chemotherapy resistance. However, despite decades of research, few predictive markers of …


Gut Microbiome-Modified Polyphenolic Compounds Inhibit Α-Synuclein Seeding And Spreading In Α-Synucleinopathies, Tritia R. Yamasaki, Kenjiro Ono, Lap Ho, Giulio M. Pasinetti May 2020

Gut Microbiome-Modified Polyphenolic Compounds Inhibit Α-Synuclein Seeding And Spreading In Α-Synucleinopathies, Tritia R. Yamasaki, Kenjiro Ono, Lap Ho, Giulio M. Pasinetti

Neurology Faculty Publications

Misfolding, aggregation and deposition of α-synuclein (α-syn) are major pathologic characteristics of Parkinson’s disease (PD) and the related synucleinopathy, multiple system atrophy (MSA). The spread of α-syn pathology across brain regions is thought to play a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that target and attenuate α-syn aggregation and spread. Recent studies of brain-penetrating polyphenolic acids, namely, 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-(3-hydroxyphenyl)propionic acid (3-HPPA) that are derived from gut microbiota metabolism of dietary polyphenols, show in vitro ability to effectively modulate α-syn misfolding, oligomerization, and …


Stroke As The Initial Presentation Of Takayasu's Arteritis: A Case Report, Paran Davari, Paige Sutton, Kimberly S. Jones May 2020

Stroke As The Initial Presentation Of Takayasu's Arteritis: A Case Report, Paran Davari, Paige Sutton, Kimberly S. Jones

Neurology Faculty Publications

In this study, we report the case of a pediatric neurology stroke patient who was ultimately diagnosed with Takayasu's Arteritis. Our case describes a 14-year-old Hispanic female with no significant past medical history who presented to an outside hospital for acute onset of confusion and right sided weakness. She was given tissue plasminogen activator (TPA) at the outside hospital and transferred as a stroke alert. Initial The NIH stroke scale (NIHSS) was 12 with primarily right sided symptoms. Physical exam was also significant for asymmetric pulses and blood pressures. Imaging was significant for multifocal stenosis. She was ultimately diagnosed with …


The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern May 2020

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …


Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich Apr 2020

Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich

Physiology Faculty Publications

Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer's disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles …


Association Of A Simplified Finnegan Neonatal Abstinence Scoring Tool With The Need For Pharmacologic Treatment For Neonatal Abstinence Syndrome, Lori A. Devlin, Janis L. Breeze, Norma Terrin, Enrique Gomez Pomar, Henrietta S. Bada, Loretta P. Finnegan, Kevin E. O'Grady, Hendrée E. Jones, Barry Lester, Jonathan M. Davis Apr 2020

Association Of A Simplified Finnegan Neonatal Abstinence Scoring Tool With The Need For Pharmacologic Treatment For Neonatal Abstinence Syndrome, Lori A. Devlin, Janis L. Breeze, Norma Terrin, Enrique Gomez Pomar, Henrietta S. Bada, Loretta P. Finnegan, Kevin E. O'Grady, Hendrée E. Jones, Barry Lester, Jonathan M. Davis

Pediatrics Faculty Publications

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment.

Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision.

Design, Setting, and Participants: This multisite cohort study included 424 neonates …


First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill Apr 2020

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …


Optimizing The Double-Row Construct: An Untied Medial Row Demonstrates Equivalent Mean Contact Pressures In A Rotator Cuff Model, Austin V. Stone, T. David Luo, Aman Sharma, Kerry A. Danelson, Michael De Gregorio, Michael T. Freehill Apr 2020

Optimizing The Double-Row Construct: An Untied Medial Row Demonstrates Equivalent Mean Contact Pressures In A Rotator Cuff Model, Austin V. Stone, T. David Luo, Aman Sharma, Kerry A. Danelson, Michael De Gregorio, Michael T. Freehill

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: The merits of a double-row rotator cuff repair (RCR) construct are well-established for restoration of the footprint and lateral-row security. The theoretical benefit of leaving the medial row untied is to prevent damage to the rotator cuff by tissue strangulation, and the benefit of suture tape is a more even distribution of force across the repair site. These benefits, to our knowledge, have not been evaluated in the laboratory.

Hypothesis: Leaving the medial row untied and using a suture bridge technique with suture tape will offer more even pressure distribution across the repair site without compromising total contact force. …


Perinatal Drug Abuse And Neonatal Drug Withdrawal, Samarth Shukla, Lisa B. Zirkin, Enrique Gomez Pomar Apr 2020

Perinatal Drug Abuse And Neonatal Drug Withdrawal, Samarth Shukla, Lisa B. Zirkin, Enrique Gomez Pomar

Pediatrics Faculty Publications

Drug abuse and addiction have significantly increased over the last few decades; specifically, opioid abuse and dependence have increased to epidemic proportions. This increased use of drugs includes women of childbearing age and those who are pregnant. Drug abuse during pregnancy is a serious health risk for both mother and newborn infant. Infants exposed to maternal drugs in fetal life develop signs of drug withdrawal during early neonatal life. This group of withdrawal signs is known as neonatal abstinence syndrome (NAS). Although NAS is not a fatal condition, it results in significant illness and prolonged hospitalization.


Protection Against Ionizing Radiation And Chemotherapy Toxicity Via Latexin Regulation, Gary Van Zant, Ying Liang, Yi Liu Mar 2020

Protection Against Ionizing Radiation And Chemotherapy Toxicity Via Latexin Regulation, Gary Van Zant, Ying Liang, Yi Liu

Internal Medicine Faculty Patents

The present invention relates to methods for protecting against damage caused by radiation and/or chemotherapy, and methods for treating bone marrow damage by reducing/ inhibiting Latexin expression and/or Latexin activity. The methods comprise administering to a subject in need thereof a pharmaceutical composition comprising an antagonist that reduces expression and/or activity of latexin, wherein latexin is a latexin polynucleotide variant and/or a latexin polypeptide variant that binds to the antagonist.


Using Medical Claims Database To Develop A Population Disease Progression Model For Leuprorelin-Treated Subjects With Hormone-Sensitive Prostate Cancer, Yixuan Zou, Fei Tang, Jeffery C. Talbert, Chee M. Ng Mar 2020

Using Medical Claims Database To Develop A Population Disease Progression Model For Leuprorelin-Treated Subjects With Hormone-Sensitive Prostate Cancer, Yixuan Zou, Fei Tang, Jeffery C. Talbert, Chee M. Ng

Pharmacy Practice and Science Faculty Publications

Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormone-sensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to …