Georgia Shelton | Washington University in St. Louis (original) (raw)
Uploads
Papers by Georgia Shelton
Stroke
Background: Neurologic patients transferred to an intensive care unit (ICU) have increased length... more Background: Neurologic patients transferred to an intensive care unit (ICU) have increased length of stays, mortality, and healthcare cost. There is limited data regarding incident transfers in stroke-specific cohorts. We sought to identify clinical features, transfer timing, and outcomes of patients admitted with ischemic stroke who required ICU escalation. Methods: We identified all patients age >18 admitted to our institution with a principle diagnosis of ischemic stroke between 2016 and 2019. We included patients requiring transfer to an ICU at any point in their hospitalization. We identified indications for transfer (IFT), time to ICU transfer (TTI), and outcomes at discharge and at 90-days post-discharge. We subdivided the IFT into neurologic and non-neurologic etiologies, and used chi-square testing and Kaplan-Meier curves with log-rank modeling to identify differences between patients with neurologic and non-neurologic transfer indications. Results: 3176 patients were ad...
Circulation, 2017
Introduction: One third of adults in the US have NAFLD, a disease characterized by accumulation o... more Introduction: One third of adults in the US have NAFLD, a disease characterized by accumulation of triglycerides (TG) in the liver. NAFLD is an independent risk factor for coronary artery disease. ...
Journal of Visualized Experiments
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclero... more Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.
Circulation, 2015
Background: There is limited information regarding genetic contributions to atherosclerotic aorti... more Background: There is limited information regarding genetic contributions to atherosclerotic aortic calcification, an important predictor of cardiovascular disease. Methods: We conducted a genome-wide association study (GWAS) meta-analysis with subsequent replication analysis to define single nucleotide polymorphisms (SNPs) associated with abdominal (AAC) or thoracic aortic calcification (TAC). AAC and TAC were quantified using multi-detector computed tomography. SNPs were assayed by Illumina or Affymetrix arrays and imputation at the cohort level was performed using data from the 1000 Genomes project. Results: 9417 individuals of European descent from four cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium were included in the AAC discovery analysis and 8422 individuals from five cohorts in the TAC discovery analysis. SNPs achieving genome-wide significance were tested for replication in four additional cohorts with Hispanic-American (HA) ...
References http://rsbl.royalsocietypublishing.org/content/10/5/20140187.full.html#ref-list-1 This... more References http://rsbl.royalsocietypublishing.org/content/10/5/20140187.full.html#ref-list-1 This article cites 16 articles, 2 of which can be accessed free Subject collections (748 articles) ecology (721 articles) behaviour Articles on similar topics can be found in the following collections Email alerting service here right-hand corner of the article or click Receive free email alerts when new articles cite this article sign up in the box at the top
Scientific Reports
Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone m... more Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMp inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of nAfLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. these data show that BMp signaling is an important determinant of nAfLD in a murine model and is associated with nAfLD in humans. The prevalence of non-alcoholic fatty liver disease (NAFLD) in adults exceeds 30% in Western countries and NAFLD portends increased risk of cardiovascular disease 1-3. The prevalence of NAFLD is particularly high among individuals with diabetes mellitus, exceeding 70% in some populations 4,5. NAFLD encompasses a spectrum of disorders ranging from simple hepatic steatosis without inflammation to steatosis with inflammation (non-alcoholic steatohepatitis) to hepatic fibrosis and cirrhosis 6,7. Despite the enormous scale of morbidity and mortality associated with NAFLD, treatments are limited to risk factor modification including lifestyle intervention and management of co-morbid metabolic disease. Currently, there are no FDA-approved pharmacotherapies for NAFLD. The pathophysiology of NAFLD involves the accumulation of neutral lipids, predominantly triglycerides, in the liver 8. Diacylglycerol O-acyltransferase 2 (DGAT2) catalyzes the conversion of diacylglycerol (DAG) to triglyceride 9. DAG is the precursor for many end products and DGAT2 is responsible for committing hepatic DAG to triglyceride 10,11. Altering DGAT2 expression or activity in vivo via pharmacologic inhibition or genetic knockdown, knockout, or overexpression leads to alterations in hepatic triglyceride content 12-18. Thus, DGAT2 expression is thought to be central to the hepatic accumulation of triglyceride in NAFLD.
Journal of Visualized Experiments, 2016
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclero... more Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.
Biology letters
Parents defend their young in many ways, including provisioning chemical defences. Recent work in... more Parents defend their young in many ways, including provisioning chemical defences. Recent work in a poison frog system offers the first example of an animal that provisions its young with alkaloids after hatching or birth rather than before. But it is not yet known whether maternally derived alkaloids are an effective defence against offspring predators. We identified the predators of Oophaga pumilio tadpoles and conducted laboratory and field choice tests to determine whether predators are deterred by alkaloids in tadpoles. We found that snakes, spiders and beetle larvae are common predators of O. pumilio tadpoles. Snakes were not deterred by alkaloids in tadpoles. However, spiders were less likely to consume mother-fed O. pumilio tadpoles than either alkaloid-free tadpoles of the red-eyed treefrog, Agalychnis callidryas, or alkaloid-free O. pumilio tadpoles that had been hand-fed with A. callidryas eggs. Thus, maternally derived alkaloids reduce the risk of predation for tadpoles,...
Stroke
Background: Neurologic patients transferred to an intensive care unit (ICU) have increased length... more Background: Neurologic patients transferred to an intensive care unit (ICU) have increased length of stays, mortality, and healthcare cost. There is limited data regarding incident transfers in stroke-specific cohorts. We sought to identify clinical features, transfer timing, and outcomes of patients admitted with ischemic stroke who required ICU escalation. Methods: We identified all patients age >18 admitted to our institution with a principle diagnosis of ischemic stroke between 2016 and 2019. We included patients requiring transfer to an ICU at any point in their hospitalization. We identified indications for transfer (IFT), time to ICU transfer (TTI), and outcomes at discharge and at 90-days post-discharge. We subdivided the IFT into neurologic and non-neurologic etiologies, and used chi-square testing and Kaplan-Meier curves with log-rank modeling to identify differences between patients with neurologic and non-neurologic transfer indications. Results: 3176 patients were ad...
Circulation, 2017
Introduction: One third of adults in the US have NAFLD, a disease characterized by accumulation o... more Introduction: One third of adults in the US have NAFLD, a disease characterized by accumulation of triglycerides (TG) in the liver. NAFLD is an independent risk factor for coronary artery disease. ...
Journal of Visualized Experiments
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclero... more Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.
Circulation, 2015
Background: There is limited information regarding genetic contributions to atherosclerotic aorti... more Background: There is limited information regarding genetic contributions to atherosclerotic aortic calcification, an important predictor of cardiovascular disease. Methods: We conducted a genome-wide association study (GWAS) meta-analysis with subsequent replication analysis to define single nucleotide polymorphisms (SNPs) associated with abdominal (AAC) or thoracic aortic calcification (TAC). AAC and TAC were quantified using multi-detector computed tomography. SNPs were assayed by Illumina or Affymetrix arrays and imputation at the cohort level was performed using data from the 1000 Genomes project. Results: 9417 individuals of European descent from four cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium were included in the AAC discovery analysis and 8422 individuals from five cohorts in the TAC discovery analysis. SNPs achieving genome-wide significance were tested for replication in four additional cohorts with Hispanic-American (HA) ...
References http://rsbl.royalsocietypublishing.org/content/10/5/20140187.full.html#ref-list-1 This... more References http://rsbl.royalsocietypublishing.org/content/10/5/20140187.full.html#ref-list-1 This article cites 16 articles, 2 of which can be accessed free Subject collections (748 articles) ecology (721 articles) behaviour Articles on similar topics can be found in the following collections Email alerting service here right-hand corner of the article or click Receive free email alerts when new articles cite this article sign up in the box at the top
Scientific Reports
Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone m... more Non-alcoholic fatty liver disease (NAFLD) affects over 30% of adults in the United States. Bone morphogenetic protein (BMP) signaling is known to contribute to hepatic fibrosis, but the role of BMP signaling in the development of NAFLD is unclear. In this study, treatment with either of two BMP inhibitors reduced hepatic triglyceride content in diabetic (db/db) mice. BMp inhibitor-induced decrease in hepatic triglyceride levels was associated with decreased mRNA encoding Dgat2, an enzyme integral to triglyceride synthesis. Treatment of hepatoma cells with BMP2 induced DGAT2 expression and activity via intracellular SMAD signaling. In humans we identified a rare missense single nucleotide polymorphism in the BMP type 1 receptor ALK6 (rs34970181;R371Q) associated with a 2.1-fold increase in the prevalence of nAfLD. In vitro analyses revealed R371Q:ALK6 is a previously unknown constitutively active receptor. these data show that BMp signaling is an important determinant of nAfLD in a murine model and is associated with nAfLD in humans. The prevalence of non-alcoholic fatty liver disease (NAFLD) in adults exceeds 30% in Western countries and NAFLD portends increased risk of cardiovascular disease 1-3. The prevalence of NAFLD is particularly high among individuals with diabetes mellitus, exceeding 70% in some populations 4,5. NAFLD encompasses a spectrum of disorders ranging from simple hepatic steatosis without inflammation to steatosis with inflammation (non-alcoholic steatohepatitis) to hepatic fibrosis and cirrhosis 6,7. Despite the enormous scale of morbidity and mortality associated with NAFLD, treatments are limited to risk factor modification including lifestyle intervention and management of co-morbid metabolic disease. Currently, there are no FDA-approved pharmacotherapies for NAFLD. The pathophysiology of NAFLD involves the accumulation of neutral lipids, predominantly triglycerides, in the liver 8. Diacylglycerol O-acyltransferase 2 (DGAT2) catalyzes the conversion of diacylglycerol (DAG) to triglyceride 9. DAG is the precursor for many end products and DGAT2 is responsible for committing hepatic DAG to triglyceride 10,11. Altering DGAT2 expression or activity in vivo via pharmacologic inhibition or genetic knockdown, knockout, or overexpression leads to alterations in hepatic triglyceride content 12-18. Thus, DGAT2 expression is thought to be central to the hepatic accumulation of triglyceride in NAFLD.
Journal of Visualized Experiments, 2016
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclero... more Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.
Biology letters
Parents defend their young in many ways, including provisioning chemical defences. Recent work in... more Parents defend their young in many ways, including provisioning chemical defences. Recent work in a poison frog system offers the first example of an animal that provisions its young with alkaloids after hatching or birth rather than before. But it is not yet known whether maternally derived alkaloids are an effective defence against offspring predators. We identified the predators of Oophaga pumilio tadpoles and conducted laboratory and field choice tests to determine whether predators are deterred by alkaloids in tadpoles. We found that snakes, spiders and beetle larvae are common predators of O. pumilio tadpoles. Snakes were not deterred by alkaloids in tadpoles. However, spiders were less likely to consume mother-fed O. pumilio tadpoles than either alkaloid-free tadpoles of the red-eyed treefrog, Agalychnis callidryas, or alkaloid-free O. pumilio tadpoles that had been hand-fed with A. callidryas eggs. Thus, maternally derived alkaloids reduce the risk of predation for tadpoles,...