Medicine and Health Sciences Commons^™

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Friendly Fire: Biological Functions And Consequences Of Chromosomal Targeting By Crispr-Cas Systems, Gary E. Heussler, George A. O'Toole

Dartmouth Scholarship

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) systems in bacteria and archaea target foreign elements, such as bacteriophages and conjugative plasmids, through the incorporation of short sequences (termed spacers) from the foreign element into the CRISPR array, thereby allowing sequence-specific targeting of the invader. Thus, CRISPR-Cas systems are typically considered a microbial adaptive immune system. While many of these incorporated spacers match targets on bacteriophages and plasmids, a noticeable number are derived from chromosomal DNA. While usually lethal to the self-targeting bacteria, in certain circumstances, these self-targeting spacers can have profound effects in regard to microbial biology, including functions …

Secreted Herpes Simplex Virus-2 Glycoprotein G Alters Thermal Pain Sensitivity By Modifying Ngf Effects On Trpv1, Jorge Rubén Cabrera, Abel Viejo-Borbolla, Antonio Alcamí, Francisco Wandosell

Dartmouth Scholarship

Genital herpes is a painful disease frequently caused by the neurotropic pathogen herpes simplex virus type 2 (HSV-2). We have recently shown that HSV-2-secreted glycoprotein G (SgG2) interacts with and modulates the activity of the neurotrophin nerve growth factor (NGF). This interaction modifies the response of the NGF receptor TrkA, increasing NGF-dependent axonal growth. NGF is not only an axonal growth modulator but also an important mediator of pain and inflammation regulating the amount, localization, and activation of the thermal pain receptor transient receptor potential vanilloid 1 (TRPV1). In this work, we addressed whether SgG2 could contribute to HSV-2-induced pain. …

Pilz Domain Protein Flgz Mediates Cyclic Di-Gmp-Dependent Swarming Motility Control In Pseudomonas Aeruginosa, Amy Baker, Andreas Diepold, Sherry Kuchma, Jessie Scott, Dae Gon Ha, Giulia Orazi, Judith Armitage, George A. O'Toole

Dartmouth Scholarship

The second messenger cyclic diguanylate (c-di-GMP) is an important regulator of motility in many bacterial species. In Pseudomonas aeruginosa, elevated levels of c-di-GMP promote biofilm formation and repress flagellum-driven swarming motility. The rotation of P. aeruginosa's polar flagellum is controlled by two distinct stator complexes, MotAB, which cannot support swarming motility, and MotCD, which promotes swarming motility. Here we show that when c-di-GMP levels are elevated, swarming motility is repressed by the PilZ domain-containing protein FlgZ and by Pel polysaccharide production. We demonstrate that FlgZ interacts specifically with the motility-promoting stator protein MotC in a c-di-GMP-dependent manner and that a …

Detecting Gene-Gene Interactions Using A Permutation-Based Random Forest Method, Jing Li, James D. Malley, Angeline S. Andrew, Margaret R. Karagas, Jason H. Moore

Dartmouth Scholarship

Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions.

Blunt Abdominal Trauma With Handlebar Injury: A Rare Cause Of Traumatic Amputation Of The Appendix Associated With Acute Appendicitis, Amanda Jensen, Reto Baertschiger, Jodi Hackworth, Fredrick Rescorla

Dartmouth Scholarship

We describe traumatic appendicitis in a 7-year-old boy who presented after sustaining blunt abdominal trauma to his right lower abdomen secondary to bicycle handlebar injury. With diffuse abdominal pain following injury, he was admitted for observation. Computed axial tomography (CT) obtained at an outside hospital demonstrated moderate stranding of the abdomen in the right lower quadrant. The CT was non-contrasted and therefore significant appendiceal distention could not be confirmed. However, there was a calcified structure in the right pelvis with trace amount of free fluid. Patient was observed with conservative management and over the course of 15 h his abdominal …

Vegfr2 Py949 Signalling Regulates Adherens Junction Integrity And Metastatic Spread, Xiujuan Li, Narendra Padhan, Elisabet O. Sjöström, Francis P. Roche, Chiara Testini, Naoki Honkura, Miguel Sáinz-Jaspeado, Emma Gordon, Katie Bentley, Andrew Philippides, Vladimir Tolmachev, Elisabetta Dejana, Radu V. Stan, Dietmar Vestweber, Kurt Ballmer-Hofer, Christer Betsholtz, Kristian Pietras, Leif Jansson, Lena Claesson-Welsh

Dartmouth Scholarship

The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2^Y949F/Y949F leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2^Y949F/Y949F mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2^Y949F/Y949F mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory …

The Inhibitory Site Of A Diguanylate Cyclase Is A Necessary Element For Interaction And Signaling With An Effector Protein, Kurt M. Dahlstrom, Krista M. Giglio, Holger Sondermann, George A. O'Toole

Dartmouth Scholarship

Many bacteria contain large cyclic diguanylate (c-di-GMP) signaling networks made of diguanylate cyclases (DGCs) and phosphodiesterases that can direct cellular activities sensitive to c-di-GMP levels. While DGCs synthesize c-di-GMP, many DGCs also contain an autoinhibitory site (I-site) that binds c-di-GMP to halt excess production of this small molecule, thus controlling the amount of c-di-GMP available to bind to target proteins in the cell. Many DGCs studied to date have also been found to signal for a specific c-di-GMP-related process, and although recent studies have suggested that physical interaction between DGCs and target proteins may provide this signaling fidelity, the importance …

Muscle Strength, Physical Activity, And Functional Limitations In Older Adults With Central Obesity, Cassandra M. Germain, John A. Batsis, Elizabeth Vasquez, Douglas R. Mcquoid

Dartmouth Scholarship

Background: Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA) and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods: Prevalence and odds of physical (PL), ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and …

Expression Of Complement And Toll-Like Receptor Pathway Genes Is Associated With Malaria Severity In Mali: A Pilot Case Control Study, Rafal S. Sobota, Antoine Dara, Jessica E. Manning, Amadou Niangaly

Dartmouth Scholarship

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood.

Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression …

Smn Protein Can Be Reliably Measured In Whole Blood With An Electrochemiluminescence (Ecl) Immunoassay: Implications For Clinical Trials, Phillip Zaworski, Katharine M. Von Herrmann, Shannon Taylor, Sara S. Sunshine, Kathleen Mccarthy, Nicole Risher, Tara Newcomb, Marla Weetall, Thomas W. Prior, Kathryn J. Swoboda, Karen S. Chen, Sergey Paushkin

Dartmouth Scholarship

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, …

Improving Cell Mixture Deconvolution By Identifying Optimal Dna Methylation Libraries (Idol), Devin C. Koestler, Meaghan J. Jones, Joseph Usset, Brock C. Christensen, Rondi A. Butler, Michael S. Kobor, John K. Weincke, Karl T. Kelsey

Dartmouth Scholarship

Background:

Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogenous biospecimens offer a promising solution, however the performance of such methods depends entirely on the library of methylation markers being used for deconvolution. Here, we introduce a novel algorithm for Identifying Optimal Libraries (IDOL) that dynamically scans a candidate set of cell-specific methylation markers to find libraries that optimize the accuracy of cell fraction estimates obtained from cell mixture deconvolution.

Results:

Application of IDOL to training set …

Pharmacotherapy For Chronic Insomnia: A Brief Survey Of Pcp Attitudes And Preferences, Adam J. Sorscher, Ali A. Siddiqui, Ardis Olson, Deborah J. Johnson

Dartmouth Scholarship

Purpose: To examine primary care professionals (PCP) attitudes and prescribing preferences toward hypnotic medications to treat chronic insomnia. Methods: An online survey was sent to members of the Dartmouth CO-OP, a practice-based primary care research network in Maine, Vermont, and New Hampshire. The survey begins with a case vignette of a 64-year old woman suffering from chronic insomnia. Clinicians were then presented with eight questions about management of the patient and their attitudes toward prescribing medications, focusing on benzodiazepines/benzodiazepine receptor agonists (BDZ/BZRAs). Results: 103 of 198 clinicians (52%) responded. Regarding choice of medication for the case vignette, 80% of respondents …

Rbdb, A Rhomboid Protease Critical For Srebp Activation And Virulence In Aspergillus Fumigatus, Sourabh Dhingra, Caitlin H. Kowlaski, Arsa Thammahong, Sarah R. Beattie, Katherine M. Bultman, Robert A. Cramer

Dartmouth Scholarship

SREBP transcription factors play a critical role in fungal virulence; however, the mechanisms of sterol regulatory element binding protein (SREBP) activation in pathogenic fungi remains ill-defined. Screening of the Neurospora crassa whole-genome deletion collection for genes involved in hypoxia responses identified a gene for an uncharacterized rhomboid protease homolog, rbdB, required for growth under hypoxic conditions. Loss of rbdB in Aspergillus fumigatus also inhibited growth under hypoxic conditions. In addition, the A. fumigatus ΔrbdB strain also displayed phenotypes consistent with defective SREBP activity, including increased azole drug susceptibility, reduced siderophore production, and full loss of virulence. Expression of …

Perceived Neighborhood Environmental Attributes Associated With Walking And Cycling For Transport Among Adult Residents Of 17 Cities In 12 Countries: The Ipen Study, Jacqueline Kerr, Jennifer A. Emond, Hannah Badland, Rodrigo Reis, Olga Sarmiento, Jordan Carlson, James F. Sallis, Ester Cerin, Kelli Cain, Terry Conway

Dartmouth Scholarship

Introduction

Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions.

Objectives

The aim of this study was to examine the strength and shape of the relationship between adults’ neighborhood perceptions and walking and cycling for transport across diverse environments.

Methods

As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18–65 years) living in physically and socially diverse neighborhoods in …

Costs Of Diagnostic And Preoperative Workup With And Without Breast Mri In Older Women With A Breast Cancer Diagnosis, Tracy Onega, Anna N.A Tosteson, Julie Weiss, Jennifer Alford-Teaster, Rebecca A. Hubbard, Louise M. Henderson, Karla Kerlikowske, Martha E. Goodrich, Cristina O'Donoghue, Karen J. Wernli, Wendy B. Demartini, Beth A. Virnig

Dartmouth Scholarship

Background: Breast cancer in the U.S. - estimated at 232,670 incident cases in 2014 - has the highest aggregate economic burden of care relative to other female cancers. Yet, the amount of cost attributed to diagnostic/ preoperative work up has not been characterized. We examined the costs of imaging and biopsy among women enrolled in Medicare who did and did not receive diagnostic/preoperative Magnetic Resonance Imaging (MRI). Methods: Using Surveillance, Epidemiology and End Results (SEER)- Medicare data, we compared the per capita costs (PCC) based on amount paid, between diagnosis date and primary surgical treatment for a breast cancer diagnosis …

Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli

Dartmouth Scholarship

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression …

Perceptions And Experiences Of Perinatal Mental Disorders In Rural, Predominantly Ethnic Minority Communities In Northern Vietnam, Daniel Abrams, Liem T. Nguyen, Jill Murphy, Younji Lee, Nhu K. Tran, David Wiljer

Dartmouth Scholarship

Background: Preliminary research has suggested that perinatal mental disorders (PMDs), including post-partum depression, are prevalent in Vietnam. However the extent to which these disorders are recognized at the community level remains largely undocumented in the literature. PMDs have also never been investigated within Vietnam’s significant ethnic minority populations, who are known to bear a greater burden of maternal and infant health challenges than the ethnic majority. Objective: To investigate knowledge and perceptions of PMDs and their treatments at the community level in a rural, predominantly ethnic minority region of northern Vietnam.

Herpes Simplex Virus And Interferon Signaling Induce Novel Autophagic Clusters In Sensory Neurons, Sarah Katzenell, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of trigeminal ganglia (TG), cycling between productive infection and latency. Neuronal antiviral responses are driven by type I interferon (IFN) and are crucial to controlling HSV-1 virulence. Autophagy also plays a role in this neuronal antiviral response, but the mechanism remains obscure. In this study, HSV-1 infection of murine TG neurons triggered unusual clusters of autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. Treatment of neurons with IFN-β induced a similar response, and cluster formation by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. The autophagic …

Validating The Children’S Depression Inventory In The Context Of Rwanda, Agnes Binagwaho, Mary C. Smith Fawzi, Mawuena Agbonyitor, Sabin Nsanzimana, Corine Karema, Eric Remera, Vincent Mutabazi, Cyprien Shyirambere, Patrick Cyamatare, Cameron Nutt, Claire Wagner, Jeanine Condo, Nancy Misago, Yvonne Kayiteshonga

Dartmouth Scholarship

Background:

Depression is often co-morbid with chronic conditions, and when combined with HIV it can increase progression and reduce survival. A brief and accurate screening tool for depression among children living with HIV is necessary to increase access to mental health care and improve HIV-related outcomes in the long-term.

Methods:

A validation study was conducted, comparing the Children’s Depression Inventory (CDI) with a structured clinical assessment as the gold standard among children living with HIV ages 7-14 years in Rwanda. The response rate was 87 % and the analysis was performed among 100 study participants.

Results:

Twenty-five percent of children …

The Economic Burden Attributable To A Child’S Inpatient Admission For Diarrheal Disease In Rwanda, Fidele Ngabo, Mercy Mvundura, Lauren Gazley, Maurice Gatera, Celse Rugambwa, Eugene Kayonga, Yvette Tuyishme, Jeanne Niyibaho, Jason M. Mwenda, Philippe Donnen, Philippe Lepage, Agnes Binagwaho, Deborah Atherly

Dartmouth Scholarship

Backround:

Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction.

Methods:

This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and …

Diabetes Pharmacotherapies And Bladder Cancer: A Medicare Epidemiologic Study, Todd A. Mackenzie, Rebecca Zaha, Jeremy Smith, Margaret R. Karagas, Nancy E. Morden

Dartmouth Scholarship

Objective:

Patients with type II diabetes have an increased risk of bladder cancer and are commonly treated with thiazolidinediones and angiotensin receptor blockers (ARBs), which have been linked to cancer risk. We explored the relationship between use of one or both of these medication types and incident bladder cancer among diabetic patients (diabetics) enrolled in Medicare.

Research Design and Methods:

We constructed both a prevalent and incident retrospective cohort of pharmacologically treated prevalent diabetics enrolled in a Medicare fee-for-service plan using inpatient, outpatient (2003–2011) and prescription (2006–2011) administrative data. The association of incident bladder cancer with exposure to pioglitazone, rosiglitazone …

Is The Closest Facility The One Actually Used? An Assessment Of Travel Time Estimation Based On Mammography Facilities, Jennifer Alford-Teaster, Jane M. Lange, Rebecca A. Hubbard, Christoph I. Lee, Jennifer S. Haas, Xun Shi, Heather A. Carlos, Louise Henderson, Deirdre Hill, Anna N. A. Tosteson, Tracy Onega

Dartmouth Scholarship

Characterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access--which is a critical component of …

Intact Cohesion, Anaphase, And Chromosome Segregation In Human Cells Harboring Tumor-Derived Mutations In Stag2, Jung-Sik Kim, Xiaoyuan He, Bernardo Orr, Gordana Wutz, Victoria Hill, Jan-Michael Peters, Duane A. Compton, Todd Waldman

Dartmouth Scholarship

Somatic mutations of the cohesin complex subunit STAG2 are present in diverse tumor types. We and others have shown that STAG2 inactivation can lead to loss of sister chromatid cohesion and alterations in chromosome copy number in experimental systems. However, studies of naturally occurring human tumors have demonstrated little, if any, correlation between STAG2 mutational status and aneuploidy, and have further shown that STAG2-deficient tumors are often euploid. In an effort to provide insight into these discrepancies, here we analyze the effect of tumor-derived STAG2 mutations on the protein composition of cohesin and the expected mitotic phenotypes of STAG2 …

Identification Of Medicare Recipients At Highest Risk For Clostridium Difficile Infection In The Us By Population Attributable Risk Analysis, Erik R. Dubberke, Margaret A. Olsen, Dustin Stwalley, Ciarán P. Kelly, Dale N. Gerding, Yinong Young-Xu, Cedric Mahé

Dartmouth Scholarship

Background: Population attributable risk percent (PAR%) is an epidemiological tool that provides an estimate of the percent reduction in total disease burden if that disease could be entirely eliminated among a subpopulation. As such, PAR% is used to efficiently target prevention interventions. Due to significant limitations in current Clostridium difficile Infection (CDI) prevention practices and the development of new approaches to prevent CDI, such as vaccina- tion, we determined the PAR% for CDI in various subpopulations in the Medicare 5% random sample. Methods: This was a retrospective cohort study using the 2009 Medicare 5% random sample. Comorbidities, infections, and healthcare …

Regulation Of Stem Cell Proliferation And Cell Fate Specification By Wingless/Wnt Signaling Gradients Enriched At Adult Intestinal Compartment Boundaries, Ai Tian, Hassina Benchabane, Zhenghan Wang, Yashi Ahmed

Dartmouth Scholarship

Intestinal stem cell (ISC) self-renewal and proliferation are directed by Wnt/β-catenin signaling in mammals, whereas aberrant Wnt pathway activation in ISCs triggers the development of human colorectal carcinoma. Herein, we have utilized the Drosophila midgut, a powerful model for ISC regulation, to elucidate the mechanisms by which Wingless (Wg)/Wnt regulates intestinal homeostasis and development. We provide evidence that the Wg signaling pathway, activation of which peaks at each of the major compartment boundaries of the adult intestine, has essential functions. Wg pathway activation in the intestinal epithelium is required not only to specify cell fate near compartment boundaries during development, …

Understanding And Meeting Information Needs For Patients With Posttraumatic Stress Disorder, Bradley V. Watts, Maha H. Zayed, Hilary Llewellyn-Thomas, Paula P. Schnurr

Dartmouth Scholarship

Background:

Posttraumatic Stress Disorder (PTSD) is a commonly occurring mental illness. There are multiple treatments for PTSD that have similar effectiveness, but these treatments differ substantially in other ways. It is desirable to have well-informed patients involved in treatment choices. A patient decision aid (PtDA) is one method to achieve this goal. This manuscript describes the rationale and development of a patient decision aid (PtDA) designed for patients with PTSD.

Methods:

We conducted an informational needs assessment of veterans (n = 19) to obtain their baseline information needs prior to the development of the PtDA. We also conducted a …

Effect Of Pentavalent Rotavirus Vaccine Introduction On Hospital Admissions For Diarrhoea And Rotavirus In Children In Rwanda: A Time-Series Analysis, Fidele Ngabo, Jacqueline E. Tate, Maurice Gatera, Celse Rugambwa, Philippe Donnen, Philippe Lepage, Jason M. Mwenda, Agnes Binagwaho, Umesh D. Parashar

Dartmouth Scholarship

Background: In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. Methods: We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management …

The Gras Sensor In Staphylococcus Aureus Mediates Resistance To Host Defense Peptides Differing In Mechanisms Of Action, Siyang Chaili, Ambrose L. L. Cheung, Arnold S. Bayer, Yan Q. Xiong, Alan Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

Staphylococcus aureus uses the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). …

Use Of Macrophage Inhibitory Cytokine-1 As A Biomarker In Screening And Surveillance Of Colorectal Neoplasia, Ethan Bortniker, Joseph C. Anderson

Dartmouth Scholarship

No abstract provided.