Medicine and Health Sciences Commons^™

Updates In The Treatment Of Alzheimer's Disease, Nothing To Forget About, Jessica Greenwood

All Publications

No abstract provided.

Hacking Humans, Upgrading Homo Sapiens: The Role Of The Huntington's Disease Community And The Consequences For Life, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Strategies Employed By Community-Based Service Providers To Address Hiv-Associated Neurocognitive Challenges: A Qualitative Study, Renato M. Liboro, Sean B. Rourke, Francisco Ibanez-Carrasco, Andrew Easton, Daniel Pugh, Claudia Medina, Allan Rae, Paul A. Shuper, Lori E. Ross

Psychology Faculty Research

Background: HIV-associated neurocognitive disorders and other causes of neurocognitive challenges experienced by people living with HIV (PLWH) persist as public health concerns in developed countries. Consequently, PLWH who experience neurocognitive challenges increasingly require social support and mental health services from community-based providers in the HIV sector. Methods: Thirty-three providers from 22 AIDS service organizations across Ontario, Canada, were interviewed to determine the strategies they used to support PLWH experiencing neurocognitive difficulties. Thematic analysis was conducted to determine key themes from the interview data. Results: Three types of strategies were identified: (a) intrapersonal, (b) interpersonal, and (c) organizational. Intrapersonal strategies involved …

The Prevalence Rate Of Cigarette Smoking Among Congestive Heart Failure Patients At A Local Family Health Center, Salome Kapella-Mshigeni, Eunice Kimunai, Chad L. Cross

School of Medicine Faculty Research

Introduction: The prevalence rate of smoking is well documented in the general population, but little is known among patients with Congestive Heart Failure (CHF). The mortality rate of CHF in San Bernardino county is nearly double (18.7 per 100,000 deaths) than that of the State of California (10.8 per 100,000 deaths). There is a need to fill knowledge gaps for CHF patients and identify evidence-based interventions that will help reduce health disparities among populations. Objective: This study aimed to determine the prevalence rate of cigarette smoking among an underserved population for patients with CHF seen at a Family Health Clinic …

Use Of A Cross-Sectional Survey In The Adult Population To Characterize Persons At High-Risk For Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Khosrow Heidari, Jill Ohar, James F. Donohue, Njira Lugogo, Chelsea L. Richard, Sarojina Kanotra, David M. Mannino, Monica Kraft, Winston Liao, Charlie Strange

Internal Medicine Faculty Publications

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Methods: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥ 10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence of …

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

Discovering The Immune Cell Landscape In Ipf By Whole Lung Single Cell Transcriptomics, Jonas C. Schupp, Taylor Adams

Yale Day of Data

Single cell transcriptomes of 27 IPF, 13 COPD and 14 control lungs were established. Cells were clustered into major cell types, then the immune cells consisting of 116,057 myeloid, 4,742 B-, and 19,165 T-& NK-cells were analyzed and subclustered. Subclustering revealed IPF-associated unique gene expression profiles subpopulations that were specific to the IPF lung. For example, we could identify an IPF-specific macrophage subpopulation which showed a pro-fibrotic profile characterized by SPP1, CHIT1, CCL18, SPARC, LGMN, CTSK, and MMP9 gene expression. Antagonistically, NK- and cytotoxic T-cells revealed a significantly increased expression of the protease inhibitors A2M and PZP in the IPF …

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease Or Failed Prior Autologous Transplant In Angioimmunoblastic T-Cell Lymphoma: A Cibmtr Analysis, Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard C. Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah

Internal Medicine Faculty Publications

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

Association Between Plasma Neutrophil Gelatinase-Associated Lipocalin And Cardiac Disease Hospitalizations And Deaths In Older Women, James J.H. Chong, Richard L. Prince, Peter L. Thompson, Sujitha Thavapalachandran, Esther Ooi, Amanda Devine, E E.M. Lim, Elizabeth Byrnes, Germaine Wong, Wai H. Lim, Joshua R. Lewis

Research outputs 2014 to 2021

Background Neutrophil gelatinase-associated lipocalin ( NGAL ) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL , cardiovascular disease biomarkers, and long-term cardiac events. Methods and Results The study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease ( CHD ) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5-year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 …

A Friend Of The Huntington’S Community Receives Award For Hd Article In Influential Brazilian Magazine, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Bird's-Eye View Of The Multiple Biochemical Mechanisms That Propel Pathology Of Alzheimer's Disease: Recent Advances And Mechanistic Perspectives On How To Halt The Disease Progression Targeting Multiple Pathways., Caleb Vegh, Kyle Stokes, Dennis Ma, Darcy Wear, Jerome Cohen, Sidhartha D. Ray, Siyaram Pandey

Touro College of Pharmacy (New York) Publications and Research

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including …

Experiential Learning In Dietetics: Can Diabetes Camp Make A Difference?, Mallory Jean Mount

Theses, Dissertations and Capstones

This longitudinal qualitative case study explored the knowledge, perceptions, confidence, and empathy gained by dietetics students during experiential learning at a residential diabetes camp. Qualitative research methods were used to explore and understand participants’ experience of hands-on involvement with type one diabetes, and what they learned at camp that cannot be learned in a classroom. Data were collected over two years at Camp Kno-Koma, the diabetes camp of West Virginia. This study suggests that experiential learning at diabetes camp can make an important contribution to the overall education of dietetics students. One year of experiential learning was beneficial to participating …

Esophageal Crohn's Disease Unresponsive To Glucocorticoids, Tanureet Kochar, Matthew Krafft, Swapna Gayam

Faculty & Staff Scholarship

No abstract provided.

Intermittent Fasting In Weight Management, Alyse Engen

Physician Assistant Scholarly Project Posters

Obesity is associated with a variety of medical conditions that adversely affect metabolic and cardiovascular health. In order for health care providers to adequately educate and promote weight management, they need to be aware of the various dietary regimens and the efficacy and adverse effects associated with each. This literature review assesses the efficacy, metabolic benefits, and cardiovascular benefits of both intermittent energy restriction and continuous energy restriction from ten articles found on various databases within the past five years. The findings indicate that although not proven superior or inferior, intermittent energy restriction provides statistically similar results to continuous energy …

Comparing Rates Of Macrosomia And Neonatal Hypoglycemia Of Differing Treatment Modalities Of Gestational Diabetes Mellitus, Ashleigh Milbrath

Physician Assistant Scholarly Project Posters

Gestational diabetes mellitus (GDM) is a known potential complication that can occur during pregnancy. Unmanaged GDM can result in maternal hyperglycemia, which can cause increased neonatal complications, two of which are macrosomia and neonatal hypoglycemia. To prevent maternal hyperglycemia, treatment of GDM typically begins with dietary changes, home glucose monitoring, increased exercise patterns and other lifestyle modifications. However, if maternal hyperglycemia persists after two weeks of maternal lifestyle modifications, there are not current best practice guidelines established for the treatment of GDM. Historically, subcutaneous multiple daily dosed insulin (MDI) has been the gold standard for treatment after lifestyle modification. However, …

Aspirin Use Following Preeclampsia To Prevent Future Adverse Cardiovascular Outcomes, Kristi Bohlig

Physician Assistant Scholarly Project Posters

• Introduction: Preeclampsia during pregnancy warrants therapy with low dose aspirin. The purpose of this review is to investigate if these women are at increased future risk for cardiovascular morbidity and mortality, and if aspirin therapy prevents future cardiovascular events.

• Research Questions: Do women who had preeclampsia during pregnancy have increased future cardiovascular morbidity and mortality? • Does continued aspirin use in postpartum women, who had preeclampsia during pregnancy; decrease future cardiovascular morbidity and mortality?

• Research Methods: Literature review was conducted utilizing CINAHL, Dynamed plus and PubMed databases.

• Discussion: Many studies have found that preeclampsia does increase …

Toxic Environmental Risk Factors For Alzheimer's Disease: A Systematic Review, Oluwaseyi Olayinka, Olaniyi O. Olayinka, Brook T. Alemu, Muge Akpinar-Elci, George T. Grossberg

Community & Environmental Health Faculty Publications

There is growing evidence of a possible association between toxic environmental factors and Alzheimer’s disease (AD), a disabling neurodegenerative condition with no known cause. Previous reviews of toxic environmental factors for AD either focused on occupational exposures or used a non-systematic methodology. The objective of this systematic review is to assess the evidence on the link between AD and exposure to a variety of toxic environmental risk factors beyond the work environment. Structured database search was used to identify relevant studies. Twenty-nine eligible studies examining the effect of various toxic environmental agents including electromagnetic fields, solvents, pesticides, toxic metals, and …

Women And Hiv: Understanding And Addressing Stigma—Evidence From The Population Council, Population Council

HIV and AIDS

Over the last 20 years, the Population Council has carried out extensive work examining the intersection of stigma and gender and its impact on HIV-related outcomes. This brief summarizes key Population Council findings from a range of studies which elucidate the experiences of stigma among women and highlights avenues for addressing stigma to mitigate women’s risk and burden of HIV.

Glucagon-Like Peptide-1s Compared To Sulfonylureas In The Treatment Of Adults Diagnosed With Type Ii Diabetes Mellitus In Primary Care, Tracy Kirchner

Physician Assistant Scholarly Project Posters

Type II diabetes mellitus (T2DM) is a prevalent disease in our country. Bullard et al. (2018) report approximately 21 million adults have T2DM in the United States. “The total estimated cost of diagnosed diabetes in 2017 is $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity” (Yang et al., 2018). Treatment of T2DM is individualized to each patient based on their co-morbidities, fiscal responsibility, and route of administration options. Sulfonylureas and Glucagon-like Peptide-1s (GLP-1) are two classes of antidiabetic drugs that are available for use as second line treatment options after metformin. This review …

Understanding Pseudomonas Aeruginosa Alginate Regulation And Its Link To Chronic Lung Infections In Cystic Fibrosis Patients, Roy Al Ahmar

Theses, Dissertations and Capstones

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). This disorder results in thick lung secretions which compromise the patient’s immune system. Chronic lung infections with Pseudomonas aeruginosa biofilms is a major factor that contributes to poor outcome for clinical treatment. The overall hypothesis of this dissertation is that small colony variant and pyrimidine biosynthesis are linked with biofilm formation, alginate production is dependent on MucA proteolysis, rifaximin can be repurposed to treat biofilm infection and multiplex PCR can be used to rapidly measure the bacterial cell density in …

Pressure To Be Perfect: Eating Disorders In Sports, Genevieve Nitzsche

Writing Across the Curriculum

Eating disorders have become more prevalent in recent years as societal standards have gotten harsher. Typically, when people think about the type of people who develop eating disorders, the first thing that pops into their head is not athletes. There is an association between athletes and the need for great amounts of food to fuel their bodies. However, in sports such as wrestling and aesthetic sports, like gymnastics and figure skating, the emphasis of image and the pressure from their coaches can be extremely harmful to their mental health. This paper discusses specific statistics of the incidence of eating disorders …

Implementing A Discharge Navigator Reducing 30-Day Readmissions For Heart Failure And Sepsis Populations, Karen Weeks

Doctor of Nursing Practice (DNP) Final Clinical Projects, 2016-2019

A national focus for healthcare reform is preventing hospital readmissions. Thirty-day unplanned hospital readmissions impact patient outcomes and are costly to the healthcare system. This project explored the impact between the discharge navigator and 30-day unplanned readmissions for heart failure and sepsis populations in a 238-bed community hospital located in central Virginia. The primary aim of this discharge navigator project was to reduce 30-day readmissions for the heart failure and sepsis populations to meet the goals of the top quartile for like hospitals and the evaluation of cost avoidance for these readmissions. Heart failure and sepsis populations are high risks …

Tgf-Β Induces A Heart Failure Phenotype Via Fibroblasts Exosome Signaling, Hesham Basma, Adelaide N. Johanson, Kajari Dhar, Daniel R. Anderson, Fang Qiu, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

METHOD: Normal heart fibroblasts were treated with TGF-β with a final conc. of 2.5 ng/ml in serum free media. HF fibroblasts were also obtained from patients undergoing implantation of left ventricular assist devices. Exosomes were collected using three-step ultracentrifugation. Cardiomyocytes were co-cultured with exosomes from TGF-β-treated, HF and …

Bronchoalveolar Lavage Fluid From Copd Patients Reveals More Compounds Associated With Disease Than Matched Plasma, Eitan Halper-Stromberg, Lucas Gillenwater, Charmion Cruickshank-Quinn, Wanda Kay O'Neal, Nichole Reisdorph, Irina Petrache, Yonghua Zhuang, Wassim W. Labaki, Jeffrey L. Curtis, James Wells, Stephen I. Rennard, Katherine A. Pratte, Prescott Woodruff, Kathleen A. Stringer, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected …

It's More Than Low Bmi: Prevalence Of Cachexia And Associated Mortality In Copd, Merry-Lynn N. Mcdonald, Emiel F.M. Wouters, Erica Rutten, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Marcas Bamman, Bartolome Celli, Alvar Agusti, Ruth Tal-Singer, Craig P. Hersh, Mark Dransfield, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients. However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index. For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.

METHODS: In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation. The …