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A Therapeutic Approach For Senile Dementias: Neuroangiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and …

Being Ready To Treat Ebola Virus Disease Patients, David Brett-Major, Shevin T. Jacob, Frederique A. Jacquerioz, George F. Risi, William A. Fischer, Yasuyuki Kato, Catherine F. Houlihan, Ian Crozier, Henry Kyobe Bosa, James V. Lawler, Takuya Adachi, Sara K. Hurley, Louise E. Berry, John C. Carlson, Thomas C. Button, Susan L. Mclellan, Barbara J. Shea, Gary G. Kuniyoshi, Mauricio Ferri, Srinivas G. Murthy, Nicola Petrosillo, Francois Lamontagne, David T. Porembka, John S. Schieffelin, Lewis Rubinson, Tim O'Dempsey, Suzanne M. Donovan, Daniel G. Bausch, Robert A. Fowler, Thomas E. Fletcher

Journal Articles: Epidemiology

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and …

Prevalence Of Schistosoma Haematobium Infection Among School-Age Children In Afar Area, Northeastern Ethiopia, Abraham Degarege, Zeleke Mekonnen, Bruno Levecke, Mengistu Legesse, Yohannes Negash, Jozef Vercruysse, Berhanu Erko

Journal Articles: Epidemiology

In this study, the prevalence and intensity of Schistosoma haematobium infection was determined among school-age children living in the Middle and Lower Awash Valley, Afar Regional State of Ethiopia. Between February and May 2014, urine samples were collected from 885 school-age children (5-16 years of age) from the Middle (n = 632; 4 villages) and Lower (n = 253; 3 villages) Awash Valley. All samples were processed using urine filtration to detect and quantify S. haematobium eggs. In addition, a subset of the urine samples was tested for hematuria using a urine dipstick (n = 556). The overall prevalence was …

Patient- And Family-Centered Care Of Children In The Emergency Department., Nanette Dudley, Alice Ackerman, Kathleen M. Brown, Sally K. Snow, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee., Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Patient- and family-centered care is an approach to the planning, delivery, and evaluation of health care that is grounded in a mutually beneficial partnership among patients, families, and health care professionals. Providing patient- and family-centered care to children in the emergency department setting presents many opportunities and challenges. This revised technical report draws on previously published policy statements and reports, reviews the current literature, and describes the present state of practice and research regarding patient- and family-centered care for children in the emergency department setting as well as some of the complexities of providing such care.

Renal And Hematological Effects Of Clcf-1, A B-Cell-Stimulating Cytokine Of The Il-6 Family., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Gennochi, Timothy Fields, Ram Sharma, Ellen T. Mccarthy, Tarak Srivastava, Jos Domen, Aurélie Tormo, Jean-François Gauchat

Manuscripts, Articles, Book Chapters and Other Papers

CLCF-1 is a cytokine known for B-cell stimulation and for neurotrophic properties. We have identified CLCF-1 as a potential injurious factor in the human renal disease focal segmental glomerulosclerosis (FSGS). We investigated its effects on renal cells and renal function in in vitro and in vivo studies. Methods include measurement of the effect of CLCF-1 on phosphorylation of target molecules of the JAK/STAT pathway, on cytoskeleton and cell morphology in cultured podocytes, on albumin permeability of isolated rat glomeruli, and on tissue phosphorylation and urine albumin after acute or chronic CLCF-1 injection. In addition, cell sorting was performed to determine …

Passing Crisis And Emergency Risk Communications: The Effects Of Communication Channel, Information Type, And Repetition., Judy Edworthy, Elizabeth Hellier, Lex Newbold, Kirsteen Titchener

School of Psychology

Three experiments explore several factors which influence information transmission when warning messages are passed from person to person. In Experiment 1, messages were passed down chains of participants using five different modes of communication. Written communication channels resulted in more accurate message transmission than verbal. In addition, some elements of the message endured further down the chain than others. Experiment 2 largely replicated these effects and also demonstrated that simple repetition of a message eliminated differences between written and spoken communication. In a final field experiment, chains of participants passed information however they wanted to, with the proviso that half …

Companion Diagnostics At The Intersection Of Personalized Medicine And Healthcare Delivery., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This article has been peer reviewed. It is the authors' final version prior to publication in Biomarkers in Medicine, Volume 9, Issue 1, January 2015, Pages 1-3.

The published version is available at DOI: 10.2217/bmm.14.99. Copyright © Future Medicine

Endgame For Polio Eradication? Options For Overcoming Social And Political Factors In The Progress To Eradicating Polio., Pavan Ganapathiraju, Christiaan B Morssink, James D. Plumb

College of Population Health Faculty Papers

In 1988, the Global Polio Eradication Initiative (GPEI) was launched with the goal of eradicating polio by the year 2000. After 25 years, several dynamics still challenge this large public health campaign with new cases of polio being reported annually. We examine the roots of this initiative to eradicate polio, its scope, the successes and setbacks during the last 25 years and reflect on the current state of affairs. We examine the social and political factors that are barriers to polio eradication. Options are discussed for solving the current impasse of polio eradication: using force, respecting individual freedoms and gaining …

Outcome Predictability Biases Learning., Oren Griffiths, Chris J. Mitchell, Anna Bethmont, Peter F. Lovibond

School of Psychology

Much of contemporary associative learning research is focused on understanding how and when the associative history of cues affects later learning about those cues. Very little work has investigated the effects of the associative history of outcomes on human learning. Three experiments extended the "learned irrelevance" paradigm from the animal conditioning literature to examine the influence of an outcome's prior predictability on subsequent learning of relationships between cues and that outcome. All 3 experiments found evidence for the idea that learning is biased by the prior predictability of the outcome. Previously predictable outcomes were readily associated with novel predictive cues, …

Multi-Parametric Mri And Texture Analysis To Visualize Spatial Histologic Heterogeneity And Tumor Extent In Glioblastoma., Leland S Hu, Shuluo Ning, Jennifer M Eschbacher, Nathan Gaw, Amylou C Dueck, Kris A Smith, Peter Nakaji, Jonathan Plasencia, Sara Ranjbar, Stephen J Price, Nhan Tran, Joseph Loftus, Robert Jenkins, Brian P O'Neill, William Elmquist, Leslie C Baxter, Fei Gao, David Frakes, John P Karis, Christine Zwart, Kristin R Swanson, Jann Sarkaria, Teresa Wu, J Ross Mitchell, Jing Li

Neurosurgery

BACKGROUND: Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.

METHODS: We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, …

Best Practices For Improving Flow And Care Of Pediatric Patients In The Emergency Department., Isabel Barata, Kathleen M. Brown, Laura Fitzmaurice, Elizabeth Stone Griffin, Sally K. Snow, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee, Gregory P. Conners, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine

Manuscripts, Articles, Book Chapters and Other Papers

This report provides a summary of best practices for improving flow, reducing waiting times, and improving the quality of care of pediatric patients in the emergency department.

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

All Dugoni School of Dentistry Faculty Articles

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …

A Review Of Locomotion Systems For Capsule Endoscopy, Lejie Liu,, Shahrzad Towfighian, Amine Hila

Mechanical Engineering Faculty Scholarship

Wireless capsule endoscopy for gastrointestinal (GI) tract is a modern technology that has the potential to replace conventional endoscopy techniques. Capsule endoscopy is a pill-shaped device embedded with a camera, a coin battery, and a data transfer. Without a locomotion system, this capsule endoscopy can only passively travel inside the GI tract via natural peristalsis, thus causing several disadvantages such as inability to control and stop, and risk of capsule retention. Therefore, a locomotion system needs to be added to optimize the current capsule endoscopy. This review summarizes the state-of-the-art locomotion methods along with the desired locomotion features such as …

Gene Expression Changes Reflect Clinical Response In A Placebo-Controlled Randomized Trial Of Abatacept In Patients With Diffuse Cutaneous Systemic Sclerosis, Eliza F. Chakravarty, Viktor Martyanov, David Fiorentino, Tammara A. Wood, David J. Haddon, Justin A. Jarrell, Paul Utz, Mark Genovese, Michael Whitfield, Lorinda Chung

Dartmouth Scholarship

Systemic sclerosis is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic.

Medical Versus Surgical Methods Of Early Abortion: Protocol For A Systematic Review And Environmental Scan Of Patient Decision Aids, Kyla Z. Donnelly, Rachel Thompson

Dartmouth Scholarship

Introduction: Currently, we lack understanding of the content, quality and impact of patient decision aids to support decision-making between medical and surgical methods of early abortion. We plan to undertake a systematic review of peer-reviewed literature to identify, appraise and describe the impact of early abortion method decision aids evaluated quantitatively (Part I), and an environmental scan to identify and appraise other early abortion method decision aids developed in the US (Part II).

Methods and analysis: For the systematic review, we will search PubMed, Cochrane Library, CINAHL, EMBASE and PsycINFO databases for articles describing experimental and observational studies evaluating …

Role Of Sigma-1 Receptors In Neurodegenerative Diseases, Linda Nguyen, Brandon P. Lucke-Wold, Shona A. Mookerjee, John Z. Cavendish, Matthew J. Robson, Anna L. Scandinaro, Rae R. Matsumoto

Faculty & Staff Scholarship

Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In …

Sox9 Inhibits -Trcp-Mediated Protein Degradation To Promote Nuclear Gli1 Expression And Cancer Stem Cell Properties, W. Deng, D. B. Vanderbilt, C.-C. Lin, K. H. Martin, K. M. Brundage, J. M. Ruppert

Faculty & Staff Scholarship

No abstract provided.

A Neural Reward Prediction Error Revealed By A Meta-Analysis Of Erps Using Great Grand Averages., Thomas D. Sambrook, Jeremy Goslin

School of Psychology

Economic approaches to decision making assume that people attach values to prospective goods and act to maximize their obtained value. Neuroeconomics strives to observe these values directly in the brain. A widely used valuation term in formal learning and decision-making models is the reward prediction error: the value of an outcome relative to its expected value. An influential theory (Holroyd & Coles, 2002) claims that an electrophysiological component, feedback related negativity (FRN), codes a reward prediction error in the human brain. Such a component should be sensitive to both the prior likelihood of reward and its magnitude on receipt. A …

Modular Expression Analysis Reveals Functional Conservation Between Human Langerhans Cells And Mouse Cross-Priming Dendritic Cells, Maxim N. Artyomov, Adiel Munk, Laurent Gorvel, Daniel Korenfeld, Marina Cella, Thomas Tung, Eynav Klechevsky

Open Access Publications

Characterization of functionally distinct dendritic cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species. Comparing modules derived from four human skin DC subsets and modules derived from the Immunological Genome Project database for all mouse DC subsets revealed that human Langerhans cells (LCs) and the mouse XCR1(+)CD8α(+)CD103(+) DCs shared the class I-mediated antigen processing and cross-presentation transcriptional modules that were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting …

The Role Of Vitamin D In Diabetes And Cardiovascular Disease: An Updated Review Of The Literature, Dimitrios Papandreou, Zujaja Tul Noor Hamid

All Works

© 2015 Dimitrios Papandreou and Zujaja-Tul-Noor Hamid. The dietary reference values for Vitamin D were set primarily considering its role in bone health, but with the discovery of Vitamin D receptors throughout body tissues, new links with other health conditions are now studied, such as for diabetes and cardiovascular diseases (CVD). This paper shall analyze and examine all new research studies carried out, especially in 2013-2015 regarding diabetes mellitus (DM) and cardiovascular diseases (CVD). Vast research has been carried out to establish strong relationship between Vitamin D serum levels, supplementation, diabetes, and CVD. However, the results from researches identified in …

Air Quality And Respiratory Health Among Adolescents From The United Arab Emirates, Caroline Barakat-Haddad, Sheng Zhang, Ayesha Siddiqua, Rania Dghaim

All Works

© 2015 Caroline Barakat-Haddad et al. Purpose. To examine the role of air quality in relation to chronic bronchitis, emphysema, asthma, wheeze, and dry cough among adolescents from the United Arab Emirates (UAE). Methods. A survey was administered on 6,363 adolescents from 9 UAE regions. Data consists of demographic, socioeconomic, residential, and behavioural variables, such as location of residence, residing near industry/gas stations/dumpsites/construction sites, residing near overhead power line/plants, exposure to tobacco, residential exposure, ethnicity, concern over air pollution, smoking, and purposely smelling gasoline fumes/glue/correctors/car exhaust/burning black ants. Logistic regression modeling was used to determine significant predictors of respiratory health. …

Molecular Characterization Of A Multidrug Resistance Incf Plasmid From The Globally Disseminated Escherichia Coli St131 Clone., Minh Duy Phan, Brian M. Forde, Kate M. Peters, Sohinee Sarkar, Steven Hancock, Mitchell Stanton-Cook, Zakour Nl Ben, Mathew Upton, Scott A. Beatson, Mark A. Schembri

School of Biomedical Sciences

Escherichia coli sequence type 131 (E. coli ST131) is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections. Plasmids represent a major vehicle for the carriage of antibiotic resistance genes in E. coli ST131. In this study, we determined the complete sequence and performed a comprehensive annotation of pEC958, an IncF plasmid from the E. coli ST131 reference strain EC958. Plasmid pEC958 is 135.6 kb in size, harbours two replicons (RepFIA and RepFII) and contains 12 antibiotic resistance genes (including the blaCTX-M-15 gene). We also carried out hyper-saturated transposon mutagenesis and multiplexed transposon …

The Effectiveness Of Psychosocial Intervention For Individuals With Cleft Lip And/Or Palate., Alyson Norman, Martin Persson, Nicola Stock, Nichola Rumsey, Jonathan Sandy, Andrea Waylen, Zoe Edwards, Vanessa Hammond, Lucy Partridge, Andy Ness

School of Psychology

OBJECTIVE: The aim of this review was to assess the effectiveness of different psychological interventions for children and adults with cleft lip and/or palate and their parents. DESIGN: We searched six databases including MEDLINE and EMBASE to June 2013 and checked bibliographies. We included research that evaluated any psychological intervention in studies in which at least 90% of the participants had cleft lip and/or palate or were parents of those with cleft lip and/or palate. Studies containing less than 90% were excluded unless they reported results separately for those with cleft lip and/or palate, or raw data were available upon …

Call Me Alix, Not Elix: Vowels Are More Important Than Consonants In Own-Name Recognition At 5 Months., Camillia Bouchon, Caroline Floccia, Thibaut Fux, Martine Adda-Decker, Thierry Nazzi

School of Psychology

Consonants and vowels differ acoustically and articulatorily, but also functionally: Consonants are more relevant for lexical processing, and vowels for prosodic/syntactic processing. These functional biases could be powerful bootstrapping mechanisms for learning language, but their developmental origin remains unclear. The relative importance of consonants and vowels at the onset of lexical acquisition was assessed in French-learning 5-month-olds by testing sensitivity to minimal phonetic changes in their own name. Infants' reactions to mispronunciations revealed sensitivity to vowel but not consonant changes. Vowels were also more salient (on duration and intensity) but less distinct (on spectrally based measures) than consonants. Lastly, vowel …

Enhanced Visual Statistical Learning In Adults With Autism., Matthew E. Roser, Richard N. Aslin, Rebecca Mckenzie, Daniel Zahra, József Fiser

School of Psychology

OBJECTIVE: Individuals with autism spectrum disorder (ASD) are often characterized as having social engagement and language deficiencies, but a sparing of visuospatial processing and short-term memory (STM), with some evidence of supranormal levels of performance in these domains. The present study expanded on this evidence by investigating the observational learning of visuospatial concepts from patterns of covariation across multiple exemplars. METHOD: Child and adult participants with ASD, and age-matched control participants, viewed multishape arrays composed from a random combination of pairs of shapes that were each positioned in a fixed spatial arrangement. RESULTS: After this passive exposure phase, a posttest …

Thinking About Ebola, David Brett-Major

Journal Articles: Epidemiology

No abstract provided.

Uncoupling Protein-2 Attenuates Palmitoleate Protection Against The Cytotoxic Production Of Mitochondrial Reactive Oxygen Species In Ins-1e Insulinoma Cells., Jonathan Barlow, Jensen V Hirschberg, Charles Affourtit

School of Biomedical Sciences

High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS) production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2) and that UCP2 knockdown does not …

Antibiotic-Resistant St38, St131 And St405 Strains Are The Leading Uropathogenic Escherichia Coli Clones In Riyadh, Saudi Arabia., Majed F. Alghoribi, Tarek M. Gibreel, Garry Farnham, Johani Sm Al, Hanan H. Balkhy, Mathew Upton

School of Biomedical Sciences

OBJECTIVES: We investigated the molecular epidemiology of uropathogenic Escherichia coli (UPEC) from a tertiary care hospital in Riyadh, Saudi Arabia, revealing, for the first time, the population structure of UPEC in the region. METHODS: A total of 202 UPEC isolates were recovered from hospital and community patients with urinary tract infection in December 2012 and January 2013. Strains were characterized by MLST, antibiotic susceptibility determination and virulence gene detection. RESULTS: The most common lineages were ST131 (17.3%), ST73 (11.4%), ST38 (7.4%), ST69 (7.4%), ST10 (6.4%), ST127 (5.9%), ST95 (5.4%), ST12 (3.5%), ST998 (3.5%) and ST405 (3%). ST131 and ST405 isolates …

Treatment Of Progressive Multiple Sclerosis: What Works, What Does Not, And What Is Needed., Anthony Feinstein, Jenny Freeman, Albert C. Lo

School of Health Professions

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely …

Metals In Boat Paint Fragments From Slipways, Repair Facilities And Abandoned Vessels: An Evaluation Using Field Portable Xrf., Andrew Turner, Sean Comber, Aldous B. Rees, Dimitrios Gkiokas, Kevin Solman

School of Geography, Earth and Environmental Sciences

Paint flaking off abandoned vessels or generated during boat repair is hazardous to human health and wildlife. In this study, a means of screening paint fragments using a field portable-X-ray fluorescence (FP-XRF) spectrometer is described. The technique is capable of delivering rapid, surficial measurements of Ba, Cu, Pb and Zn down to concentrations less than 150 μg g(-1), and Sn and Cr to concentrations of a few hundred μg g(-1). Application of the technique to fragments collected from slipways, yards, hardstandings, abandoned boats and ships undergoing maintenance throughout the EU reveal highly variable concentrations of metals among samples from the …