Medicine and Health Sciences Commons^™

Primordium Of An Artificial Bruch's Membrane Made Of Nanofibers For Engineering Of Retinal Pigment Epithelium Cell Monolayers, Patrick Warnke, Mohammad Alamein, Stuart Skabo, Sebastien Stephens, Robert Bourke, Peter Heiner, Qin Liu

Qin Liu

Transplanted Retinal Pigment Epithelium(RPE) cells hold promise for treatment of Age-related Macular Degeneration(AMD) and Stargardt Disease(SD), but it is conceivable that the degenerated host Bruch's membrane(BM) as a natural substrate for RPE might not optimally support transplanted cell survival with correct cellular organization. We fabricated novel ultrathin 3-dimensional(3D) nanofibrous membranes from Collagen type I and poly(lactic-co-glycolic acid) (PLGA) by an advanced clinical-grade needle-free-electrospinning process. The nanofibrillar 3D networks highly mimicked the fibrillar architecture of the native inner collagenous layer of human BM. Human RPE cells grown on our nanofibrous membranes bore striking resemblance to native human RPE. They exhibited a …

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

Deborah L Preston

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …

Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough

Deborah L Preston

Background Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading. Methods Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …

Risk And Protective Factors Associated With Health-Related Quality Of Life Among Older Gay And Bisexual Men Living With Hiv Disease, Charles A. Emlet, Karen I. Fredriksen-Goldsen

Charles Emlet

No abstract provided.

Experiences Of Community And Parental Violence Among Hiv Positive Young Racial/Ethnic Minority Men Who Have Have With Men, Sheldon D. Fields

Sheldon D. Fields

Adolescents and young adults (ages 13–24) in the USA are frequently exposed to violence in their community and home. While studies have examined the prevalence and impact of violence exposure among adolescents, there is a lack of data focusing specifically on adolescent men of color who have sex with men. Eight demonstration sites funded through a Special Projects of National Significance (SPNS) Initiative recruited 363 HIV-positive racial/ethnic minority young men who have sex with men (YMSM) for a longitudinal study between 2006 and 2009. Over two-thirds of participants (83.8%) had witnessed community violence, 55.1% in the prior three months. Witnessing …

Increase In The Proportion Of Patients Hospitalized With Acute Myocardial Infarction With Do-Not-Resuscitate Orders Already In Place Between 2001 And 2007: A Nonconcurrent Prospective Study, Jane Saczynski, Ezra Gabbay, David Mcmanus, Richard Mcmanus, Joel Gore, Jerry Gurwitz, Darleen Lessard, Robert Goldberg

Richard H. McManus

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among …

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …

Increase In The Proportion Of Patients Hospitalized With Acute Myocardial Infarction With Do-Not-Resuscitate Orders Already In Place Between 2001 And 2007: A Nonconcurrent Prospective Study, Jane Saczynski, Ezra Gabbay, David Mcmanus, Richard Mcmanus, Joel Gore, Jerry Gurwitz, Darleen Lessard, Robert Goldberg

Richard H. McManus

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among …

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Edward R Norris MD, FAPA, FAPM

No abstract provided.

A Multidisciplinary, Resident-Run Clinic For The Treatment Of Hepatitis C In An Underserved, Urban Primary Care Setting, Suzanne J. Templer Do, Joseph L. Yozviak Do, Facp, Vishal Patel Md, Edward Norris Md, Fapm, Eric J. Gertner Md, Mph

Edward R Norris MD, FAPA, FAPM

No abstract provided.

Relationship Between Plasma Glucose And Mortality In Non-Diabetic Patients With Acute Coronary Syndrome And Systolic Heart Failure: Insights From The Ephesus Trial, Prakash Deedwania Md, Ravi V. Desai Md, Marjan Mujib Md, Mph, Bertram Pitt, Ali Ahmed Md, Mph

Ravi V Desai MD

No abstract provided.

De-Branching Of The Aortic Arch During Thoracic Endovascular Aortic Repair, James K. Wu Md, Caitlin O'Connor Bs, Tim S. Misselbeck Md, Theodore G. Phillips Md

James K. Wu, M.D.

No abstract provided.

Fabry's Disease With Lvot Obstruction: Diagnosis And Management, Jacob Blount, James Wu, Matthew Martinez

James K Wu MD

A 46-year-old male was diagnosed with hypertrophic cardiomyopathy (HCM) and severe left ventricular outflow tract (LVOT) obstruction. Genetic testing revealed that this was a "mimic of HCM" and the true diagnosis was Fabry's disease, although there were no other clinical features of Fabry's. Despite maximal medical therapy he remained symptomatic from the outflow tract gradient and required surgical myectomy for symptom relief. This case illustrates the diagnosis of an HCM mimic by genetic testing.

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.

Transgenic Mosquitoes Expressing A Phospholipase A(2) Gene Have A Fitness Advantage When Fed Plasmodium Falciparum-Infected Blood, Ryan C. Smith, Christopher Kizito, Jason L. Rasgon, Marcelo Jacobs-Lorena

Ryan C. Smith

Genetically modified mosquitoes have been proposed as an alternative strategy to reduce the heavy burden of malaria. In recent years, several proof-of-principle experiments have been performed that validate the idea that mosquitoes can be genetically modified to become refractory to malaria parasite development. We have created two transgenic lines of Anophelesstephensi, a natural vector of Plasmodium falciparum, which constitutively secrete a catalytically inactive phospholipase A2 (mPLA2) into the midgut lumen to interfere with Plasmodium ookinete invasion. Our experiments show that both transgenic lines expressing mPLA2 significantly impair the development of rodent malaria parasites, but only one line impairs the development …

Sphincter-Sparing Surgery For Adenocarcinoma Of The Distal 3 Cm Of The True Rectum: Results After Neoadjuvant Therapy And Minimally Invasive Radical Surgery Or Local Excision, Dr. John Marks, Dr, George Nassif, Dr. Henry Schoonyoung, Dr. Al Denittis, Dr. Eric Zeger, Dr. Mohammed Mohiuddin, Dr. Gerald Marks

Dr. John Marks

Background Ideal treatment of rectal cancer includes controlling the cancer; minimizing trauma, morbidity, and mortality; and avoiding a colostomy with preservation of adequate function. These goals become more challenging the further distal in the rectum the cancer is located. We sought to determine whether minimally invasive sphincter-preservation surgery (SPS) can accomplish good cancer control, maintaining sphincter function with minimal morbidity and mortality in rectal cancers of the distal 3 cm after receiving neoadjuvant chemoradiotherapy.

Methods We retrospectively reviewed a prospectively maintained rectal cancer database of a single colorectal surgeon to identify all patients with cancers of the distal 3 cm …

25 Years Of Reporting Hiv: What Lessons Can Pacific Journalists Learn?, Trevor Cullen

Trevor A Cullen

No abstract provided.

Hiv/Aids And Development In The Pacific, Trevor Cullen

Trevor A Cullen

No abstract provided.

Treating Methicillin-Resistant Staphylococcus Aureus With The Drug Vancomycin In A Home Infusion Therapy Setting, Joshua Webb, Alberto Coustasse, Dennis Emmett

Dennis Emmett

The basic purpose of this paper is to examine the effects the home infusion therapy has on the cost, duration of, and effectiveness of treatment between those individuals under 60 and those 60 and over. The results show that those 60 and over had a slightly higher cost/day. The older age group had slightly smaller treatment duration, then the younger group. The number of adverse effects was small. The results suggest that home infusion therapy appears to be a viable alternative to hospitalization.

Treating Methicillin-Resistant Staphylococcus Aureus With The Drug Vancomycin In A Home Infusion Therapy Setting, Joshua L. Webb, Alberto Coustasse, Dennis Emmett

Alberto Coustasse, DrPH, MD, MBA, MPH

The basic purpose of this paper is to examine the effects the home infusion therapy has on the cost, duration of, and effectiveness of treatment between those individuals under 60 and those 60 and over. The results show that those 60 and over had a slightly higher cost/day. The older age group had slightly smaller treatment duration, then the younger group. The number of adverse effects was small. The results suggest that home infusion therapy appears to be a viable alternative to hospitalization.

The Uncertainty Of The Egfr, Tony Badrick, Peter Turner

Tony Badrick

The estimated glomerular filtration rate (eGFR) is a parameter derived from the serum creatinine, patient age and gender and is used to ascertain renal function. It is subject to variation because of the analytical error of the creatinine measurement and biological variation. The widespread use of the eGFR to classify renal disease has led to the identification of more patients with marginal chronic kidney disease but because of the uncertainty of the eGFR it has also led to over-diagnosis of some kidney disease. There is a well described age relation with eGFR.The uncertainty of the eGFR at the critical decision …

Unique Transcriptional Profile Of Sustained Ligand-Activated Preconditioning In Pre- And Post-Ischemic Myocardium, Kevin Ashton, Amanda Tupicoff, Grant Williams-Pritchard, Can Kiessling, Louise See Hoe, John Headrick, Jason Peart

Kevin Ashton

Background: Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings: Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated …

The Chronic Kidney Disease Controversy: How Expanding Definitions Care Unnecessarily Labelling Many People As Diseased, Ray Moynihan, Richard Glassock, Jenny A. Doust

Jenny Doust

Extract: In 2002 the United States Kidney Foundation launched a novel framework for defining and classifying chronic kidney disease. The framework was widely embraced because it imposed order in a chaotic landscape characterised by a variety of names, including renal insufficiency, renal impairment, and renal failure. It has had an appreciable effect on clinical care worldwide through guidelines, pay for performance measures, and sparked debate on the merits of screening programmes. However, it has also generated considerable controversy. We examine the rationale for the framework, the varying responses and controversies it has provoked, and provide advice for clinicians who are …

The Chronic Kidney Disease Controversy: How Expanding Definitions Care Unnecessarily Labelling Many People As Diseased, Ray Moynihan, Richard Glassock, Jenny A. Doust

Ray Moynihan

Extract: In 2002 the United States Kidney Foundation launched a novel framework for defining and classifying chronic kidney disease. The framework was widely embraced because it imposed order in a chaotic landscape characterised by a variety of names, including renal insufficiency, renal impairment, and renal failure. It has had an appreciable effect on clinical care worldwide through guidelines, pay for performance measures, and sparked debate on the merits of screening programmes. However, it has also generated considerable controversy. We examine the rationale for the framework, the varying responses and controversies it has provoked, and provide advice for clinicians who are …

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang

William D Thomas Jr

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of …

Selective Effects Of Intrinsic A2aar Activity On Cardiac And Coronary Injuries With Lps Challenge, Melissa Reichelt, Kevin Ashton, S Mustafa, B Tang, Catherine Ledent, Xing Tan, John Headrick, R Morrison

Kevin Ashton

We assessed the impact of A2A adenosine receptor (A2AAR) knockout (KO) on LPS-triggered cardiovascular injuries, inflammation, gene expression and mortality. LPS precipitated cardiac injury, with 7-fold elevations in serum cardiac troponin I (cTnI) and 25–35% reductions in ventricular contractility. Coronary dysfunction was evident as a 20% reduction in reactive hyperaemic flows. A2AAR KO augmented cTnI release 3-fold without modifying ventricular dysfunction. Coronary effects of LPS and A2AAR KO were identical, and LPS no longer modified hyperaemia in A2AAR KO hearts. Effects of A2AAR activity were largely independent of shifts in acute phase reactants (CRP, haptoglobin) and circulating cytokines. Thus, up …

Cardiovascular Adenosine Receptors: Expression, Actions And Interactions, John Headrick, Kevin Ashton, Roselyn Rose'meyer, Jason Peart

Kevin Ashton

Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types—A1, A2A, A2B, and A3Rs—regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory–vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The …

The Adenosine A2a Receptor — Myocardial Protectant And Coronary Target In Endotoxemia, Melissa Reichelt, Kevin Ashton, Xing Tan, S Mustafa, Catherine Ledent, Lea Delbridge, Polly Hofmann, John Headrick, R Morrison

Kevin Ashton

Background: Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation.

Methods: We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO).

Results: Cardiac injury was evident in LPS-treated WTs, with ~ 7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by …

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

Arthur M. Mercurio

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.