Medical Specialties Commons^™

Failure To Thrive Hospitalizations And Risk Factors For Readmission To Children's Hospitals., Henry T. Puls, Matt Hall, Jessica L. Bettenhausen, Matthew B. Johnson, Christina Peacock, Jean L. Raphael, Jason G. Newland, Jeffrey D. Colvin

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Risk factors for failure to thrive (FTT) readmissions, including medical complexity, have not been described. We sought to characterize children hospitalized for FTT and identify risk factors associated with FTT-specific readmissions during the current era of increasing medical complexity among hospitalized children.

METHODS: This retrospective cohort study used the Pediatric Health Information System database of 43 freestanding children's hospitals across the United States. The cohort included childrenmodels, we assessed the association of demographic, clinical, diagnostic, and treatment characteristics with FTT-specific readmission.

RESULTS: There were 10 499 FTT hospitalizations, with 14.1% being readmitted for FTT within 3 years and 4.8% …

Underuse Of Oral Anticoagulants For Nonvalvular Atrial Fibrillation: Past, Present, And Future, Ramsey M Wehbe, Ajay Yadlapati

The Texas Heart Institute Journal

No abstract provided.

Periodontitis In Chronic Heart Failure, Hanna Fröhlich, Kristina Herrmann, Jennifer Franke, Alamara Karimi, Tobias Täger, Rita Cebola, Hugo A Katus, Christian Zugck, Lutz Frankenstein

The Texas Heart Institute Journal

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause.

We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey.

Gingivitis, moderate …

Association Between High Endocardial Unipolar Voltage And Improved Left Ventricular Function In Patients With Ischemic Cardiomyopathy, Ki Park, Dejian Lai, Eileen M Handberg, Lem Moyé, Emerson C Perin, Carl J Pepine, R David Anderson

The Texas Heart Institute Journal

We know that endocardial mapping reports left ventricular electrical activity (voltage) and that these data can predict outcomes in patients undergoing traditional revascularization. Because the mapping data from experimental models have also been linked with myocardial viability, we hypothesized an association between increased unipolar voltage in patients undergoing intramyocardial injections and their subsequent improvement in left ventricular performance.

For this exploratory analysis, we evaluated 86 patients with left ventricular dysfunction, heart-failure symptoms, possible angina, and no revascularization options, who were undergoing endocardial mapping. Fifty-seven patients received bone marrow mononuclear cell (BMC) injections and 29 patients received cell-free injections of a …

Coronary-Cameral Fistula Caused By Guidewire Trauma And Resolved By Coil Embolization, Suvro Banerjee, Soumya Patra

The Texas Heart Institute Journal

A 57-year-old woman presented with effort angina. A coronary angiogram revealed critical 2-vessel disease, for which she subsequently underwent percutaneous coronary intervention. During angioplasty, a coronary guidewire-inadvertently passed into the right ventricle through the septal branches of the posterior descending coronary artery-caused a coronary artery-to-right ventricular fistula. This fistula was successfully closed percutaneously by coil embolization. To our knowledge, this is the first report of a case in which a coronary artery-to-right ventricular fistula caused by a guidewire was managed successfully by coil embolization.

Advanced Interventional Therapy For Radiation-Induced Cardiovascular Disease, Daisy C Nieto

The Texas Heart Institute Journal

This report describes the case of a 61-year-old woman who presented with dyspnea, aortic stenosis, and coronary artery disease-typical side effects of radiation therapy for Hodgkin lymphoma. A poor candidate for surgery, she underwent successful high-risk percutaneous coronary intervention and subsequent transcatheter aortic valve replacement. This report highlights some of the cardiovascular-specific sequelae of radiation therapy for cancer treatment; in addition, possible directions for future investigations are discussed.

Statins And Exercise Training Response In Heart Failure Patients: Insights From Hf-Action., Jacob P. Kelly, Allison Dunning, Phillip J. Schulte, Mona Fiuzat, Eric S. Leifer, Jerome L. Fleg, Lawton S. Cooper, Steven J. Keteyian, Dalane W. Kitzman, Ileana L. Pina, William E. Kraus, David J. Whellan, Christopher M. O'Connor, Robert J. Mentz

Division of Cardiology Faculty Papers

OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response.

BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF).

METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity …

Development Of The Chronic Obstructive Pulmonary Disease Morning Symptom Diary (Copd-Msd), Gary Globe, Brooke Currie, Nancy Kline Leidy, Paul Jones, David M. Mannino, Fernando Martinez, Paul Klekotka, Sean O'Quinn, Niklas Karlsson, Ingela Wiklund

Preventive Medicine and Environmental Health Faculty Publications

Background: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one’s ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials.

Methods: A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews ( …

Magic Study: Aims, Design And Methods Using Systemchange™ To Improve Immunosuppressive Medication Adherence In Adult Kidney Transplant Recipients., Cynthia L. Russell, Shirley Moore, Donna Hathaway, An-Lin Cheng, Guoqing Chen, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial

METHODS/DESIGN: We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed …

Exposure Of Human Lung Cells To Tobacco Smoke Condensate Inhibits The Nucleotide Excision Repair Pathway, Nathaniel C. Holcomb, Mamta Goswami, Sung Gu Han, Samuel Clark, David K. Orren, C. Gary Gairola, Isabel Mellon

Toxicology and Cancer Biology Faculty Publications

Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, …

Adverse Drug Effects And Preoperative Medication Factors Related To Perioperative Low-Dose Ketamine Infusions., Eric S. Schwenk, Stephen F. Goldberg, Ronak D. Patel, Jon Zhou, Douglas R. Adams, Jaime L. Baratta, Eugene R. Viscusi, Richard H. Epstein

Department of Anesthesiology Faculty Papers

High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions …

Structure And Functions Of Angiotensinogen, Hong Lu, Lisa A. Cassis, Craig W. Vander Kooi, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of …

Validation Of Noninvasive Measures Of Left Ventricular Mechanics In Children: A Simultaneous Echocardiographic And Conductance Catheterization Study., Shahryar M. Chowdhury, Ryan J. Butts, Carolyn L. Taylor, Varsha M. Bandisode, Karen S. Chessa, Anthony M. Hlavacek, Girish S. Shirali, G Hamilton Baker

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The accuracy of echocardiography in evaluating left ventricular contractility has not been validated in children. The objective of this study was to compare echocardiographic measures of contractility with those derived from pressure-volume loop (PVL) analysis in children.

METHODS: Patients with relatively normal loading conditions undergoing routine left heart catheterization were prospectively enrolled. PVLs were obtained via conductance catheters. The gold-standard measure of contractility, end-systolic elastance (Ees), was obtained via balloon occlusion of one or both vena cavae. Echocardiograms were performed immediately after PVL analysis under the same anesthetic conditions. Single-beat estimations of echocardiographic Ees were calculated using four different …

Characterization Of The Microbiome Of Nipple Aspirate Fluid Of Breast Cancer Survivors., Alfred A Chan, Mina Bashir, Magali N Rivas, Karen Duvall, Peter A Sieling, Thomas R Pieber, Parag A Vaishampayan, Susan M Love, Delphine J Lee

Articles, Abstracts, and Reports

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there …

The Brain Imaging Data Structure, A Format For Organizing And Describing Outputs Of Neuroimaging Experiments, Krzysztof Gorgolewski, Tibor Auer, Vince Calhoun, R Cameron Craddock, Samir Das, Eugene Duff, Guillaume Flandin, Tristan Glatard, Yaroslav Halchenko

Dartmouth Scholarship

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this …

Pik3ca-Associated Developmental Disorders Exhibit Distinct Classes Of Mutations With Variable Expression And Tissue Distribution, Ghayda Mirzaa, Andrew E Timms, Valerio Conti, Evan August Boyle, Katta M Girisha, Beth Martin, Martin Kircher, Carissa Olds, Jane Juusola, Sarah Collins, Kaylee Park, Melissa Carter, Ian Glass, Inge Krägeloh-Mann, David Chitayat, Aditi Shah Parikh, Rachael Bradshaw, Erin Torti, Stephen Braddock, Leah Burke, Sondhya Ghedia, Mark Stephan, Fiona Stewart, Chitra Prasad, Melanie Napier, Sulagna Saitta, Rachel Straussberg, Michael Gabbett, Bridget C O'Connor, Catherine E Keegan, Lim Jiin Yin, Angeline Hwei Meeng Lai, Nicole Martin, Margaret Mckinnon, Marie-Claude Addor, Luigi Boccuto, Charles E Schwartz, Agustina Lanoel, Robert L Conway, Koenraad Devriendt, Katrina Tatton-Brown, Mary Ella Pierpont, Michael Painter, Lisa Worgan, James Reggin, Raoul Hennekam, Karen Tsuchiya, Colin C Pritchard, Mariana Aracena, Karen W Gripp, Maria Cordisco, Hilde Van Esch, Livia Garavelli, Cynthia Curry, Anne Goriely, Hulya Kayserilli, Jay Shendure, John Graham, Renzo Guerrini, William B Dobyns

Articles, Abstracts, and Reports

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing ( …

3-Year Outcomes In High-Risk Patients Who Underwent Surgical Or Transcatheter Aortic Valve Replacement., G Michael Deeb, Michael J Reardon, Stan Chetcuti, Himanshu J Patel, P Michael Grossman, Steven J Yakubov, Neal S Kleiman, Joseph S Coselli, Thomas G Gleason, Joon Sup Lee, James B Hermiller, John Heiser, William Merhi, George L Zorn, Peter Tadros, Newell Robinson, George Petrossian, G Chad Hughes, J Kevin Harrison, Brijeshwar Maini, Mubashir Mumtaz, John Conte, Jon Resar, Vicken Aharonian, Thomas Pfeffer, Jae K Oh, Hongyan Qiao, David H Adams, Jeffrey J Popma

Heart and Vascular Articles

BACKGROUND: In patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival compared with surgery.

OBJECTIVES: This study sought to determine whether this clinical benefit was sustained over time.

METHODS: Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure.

RESULTS: A total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted …

Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue …

Emergency Coronary Artery Bypass Grafting: Indications And Outcomes From 2003 Through 2013, Erin M Schumer, John H Chaney, Jaimin R Trivedi, Paul L Linsky, Matthew L Williams, Mark S Slaughter

The Texas Heart Institute Journal

Emergency coronary artery bypass grafting (CABG) is associated with increased in-hospital mortality rates and adverse events. This study retrospectively evaluated indications and outcomes in patients who underwent emergency CABG.

The Society of Thoracic Surgeons database for a single center (Jewish Hospital) was queried to identify patients undergoing isolated CABG. Univariate analysis was performed.

From January 2003 through December 2013, 5,940 patients underwent CABG; 212 presented with emergency status. A high proportion of female patients (28.2%) underwent emergency surgery. Emergency CABG patients experienced high rates of intra-aortic balloon pump support, bleeding, dialysis, in-hospital death, and prolonged length of stay. The proportion …

Two Cases Of Transcatheter Closure Of Central Aortopulmonary Shunts: One With An Amplatzer Duct Occluder Ii And One With An Amplatzer Vascular Plug I, Ahmet Celebi, Ilker Kemal Yucel, Sevket Balli, Mehmet Kucuk

The Texas Heart Institute Journal

When total correction is not possible in infants who have a cyanotic congenital heart disease, creation of a palliative aortopulmonary shunt is essential. A central aortopulmonary shunt is preferable, because of its technical and hemodynamic advantages. Overcirculation, thrombosis, and stenosis of the shunt are the main postoperative sequelae that necessitate urgent reintervention. Percutaneous transcatheter closure of aortopulmonary shunts can eliminate the need for reoperation and substantially decrease postoperative morbidity and mortality rates. We report our successful transcatheter closures of central aortopulmonary shunts in a 3-month-old infant and a 15-year-old girl, with use of an Amplatzer Duct Occluder II and an …

Fresh Autologous Pericardium To Reconstruct The Pulmonary Valve At The Annulus When Tetralogy Of Fallot Requires A Transannular Patch At Midterm, Shantanu Pande, Jugal K Sharma, C R Siddartha, Anubhav Bansal, Surendra K Agarwal, Prabhat Tewari, Aditya Kapoor

The Texas Heart Institute Journal

Tetralogy of Fallot often requires reconstruction of the right ventricular outflow tract with a transannular patch (TAP), but this renders the pulmonary valve incompetent and eventually leads to right ventricular dysfunction.

We retrospectively evaluated the efficacy of a reconstructed pulmonary valve and annulus in 70 patients who underwent, from December 2006 through December 2010, complete correction of tetralogy of Fallot. We divided the 70 patients into 2 groups in accordance with whether they required (n=50) or did not require (n=20) a TAP. We used autologous untreated pericardium to fashion the TAP and to create both an annulus of the correct …

Endocarditis And Incomplete Endothelialization 12 Years After Amplatzer Septal Occluder Deployment, Allan K Nguyen, Brian A Palafox, Joanne P Starr, Richard N Gates, Farbouch Berdjis

The Texas Heart Institute Journal

A 4-year-old boy had a 15-mm atrial septal defect repaired percutaneously with use of an Amplatzer Septal Occluder. At age 16 years, he presented with a week's history of fever, chills, dyspnea, fatigue, and malaise. Cultures grew methicillin-sensitive Staphylococcus aureus. A transesophageal echocardiogram showed a 1.25 × 1.5-cm pedunculated mass on the left aspect of the atrial septum just superior to the mitral valve, and a smaller vegetation on the right inferior medial aspect of the septum. At surgery, visual examination of both sides of the septum revealed granulation tissue, the pedunculated mass, the small vegetation, and exposed metal …

Skepticism, The Trained Eye, And The Telltale Clue, Ethan A Natelson

The Texas Heart Institute Journal

No abstract provided.

Does Myocardial Necrosis Occur In Rhabdomyolysis?, Gabriel M Aisenberg, Herbert L Fred

Faculty, Staff and Student Publications

No abstract provided.

Expression And Function Of Pannexins In The Inner Ear And Hearing, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin (Panx) is a gene family encoding gap junction proteins in vertebrates. So far, three isoforms (Panx1, 2 and 3) have been identified. All of three Panx isoforms express in the cochlea with distinct expression patterns. Panx1 expresses in the cochlea extensively, including the spiral limbus, the organ of Corti, and the cochlear lateral wall, whereas Panx2 and Panx3 restrict to the basal cells of the stria vascularis in the lateral wall and the cochlear bony structure, respectively. However, there is no pannexin expression in auditory sensory hair cells. Recent studies demonstrated that like connexin gap junction gene, Panx1 deficiency …

Adiponectin Ameliorates The Apoptotic Effects Of Paraquat On Alveolar Type Ⅱ Cells Via Improvements In Mitochondrial Function., Yarong He, Liqun Zou, Yaxiong Zhou, Hai Hu, Rong Yao, Yaowen Jiang, Wayne Bond Lau, Tun Yuan, Wen Huang, Zhi Zeng, Yu Cao

Department of Emergency Medicine Faculty Papers

Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)‑induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ‑induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ‑induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of …

Calpain-5 Expression In The Retina Localizes To Photoreceptor Synapses, Kellie A. Schaefer, Marcus A. Toral, Gabriel Velez, Allison J. Cox, Sheila A. Baker, Nicholas C. Borcherding, Diana F. Colgan, Vimala Bondada, Charles B. Mashburn, Chen Guang Yu, James W. Geddes, Stephen H. Tsang, Alexander G. Bassuk, Vinit B. Mahajan

Spinal Cord and Brain Injury Research Center Faculty Publications

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments.

Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions.

Results: Most CAPN5 genetic variation occurs outside its protease core; and searches …

The Behavioral Addiction Indoor Tanning Screener (Baits): An Evaluation Of A Brief Measure Of Behavioral Addictive Symptoms, Jerod L. Stapleton, Joel J. Hillhouse, Rob Turrisi, Katie Baker, Sharon L. Manne, Elliot J. Coups

ETSU Faculty Works

No abstract provided.

Harnessing Teams And Technology To Improve Outcomes In Infants With Single Ventricle., Girish S. Shirali, Lori A. Erickson, Johnathan Apperson, Kathy Goggin, David D. Williams, Kimberly J. Reid, Andrea Bradley-Ewing, Dawn Tucker, Michael Bingler, John Spertus, Leslie Rabbitt, Richard Stroup

Manuscripts, Articles, Book Chapters and Other Papers

Infants with single ventricle require staged cardiac surgery, with stage I typically performed shortly after birth, stage II at 4 to 6 months of age, and stage III at 3 to 5 years of age. There is a high risk of interstage mortality and morbidity after infants are discharged from the hospital between stages I and II. Traditional home monitoring requires caregivers to record measurements of weight and oxygen saturation into a binder and requires families to assume a surveillance role. We have developed a tablet PC-based solution that provides secure and nearly instantaneous transfer of patient information to a …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …