Digital Commons Network^™

Doxycycline Down-Regulates Dna-Pk And Radiosensitizes Tumor Initiating Cells: Implications For More Effective Radiation Therapy., Rebecca Lamb, Marco Fiorillo, Amy Chadwick, Bela Ozsvari, Kimberly J Reeves, Duncan L Smith, Robert B Clarke, Sacha J Howell, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Md, Maria Peiris-Pagès, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline …

Behavioral Immunity Suppresses An Epizootic In Caribbean Spiny Lobsters, Mark J. Butler Iv, Donald C. Behringer Jr., Thomas W. Dolan Iii, Jessica Moss, Jeffrey D. Shields

Biological Sciences Faculty Publications

Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of "behavioral immunity"; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We …

Method Of Treating Inflammation Using Human Immunosuppressive Protein, Paul R. Sanberg, Robert W. Engelman, William R. Gower

USF Patents

A method of treating inflammation by administering a therapeutically effective amount of a human immunosuppressant protein (HISP) to a subject is presented. The inventors have discovered a novel immunosuppressive protein purified from the supernatant of hNT cell culture. The immunosuppressant protein has a molecular weight of about 40-100 kDa, an isoelectric point of about 4.4, a net ionic charge and is capable of suppressing T-cell activation, T-cell proliferation and the production of IL-2. This protein can be used in treating inflammation, preventing graft rejection after transplantation, treating autoimmune diseases and suppressing allergic responses as well as other uses.

Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa, Andrei Rajkovic, Sarah Erickson, Anne Witzky, Owen E. Branson, Jin Seo, Philip R. Gafken, Michael A. Frietas, Julian P. Whitelegge, Kym F. Faull, William Wiley Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In Escherichia coli and Salmonella enterica, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as Pseudomonas aeruginosa, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of P. aeruginosa EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to E. coli EF-P. Analysis of the genomes …

Commencement, Philadelphia (2015), Philadelphia College Of Osteopathic Medicine

Commencements

Philadelphia Campus D.O. Commencement program, 124th Class. Degrees include Doctorate in Osteopathic Medicine.

Serum Vascular Endothelial Growth Factor Vegf And Interlukin-8 As A Novel Biomarkers For Early Detection Of Ovarian Tumors, Maisaa G. Jumaa, Khalid A. Habib, Munther J. Hussein

Baghdad Science Journal

Epithelial ovarian cancer is the leading cause of cancer deaths from gynecological malignancies. Angiogenesis is considered essential for tumor growth and the development of metastases. VEGF and IL-8 are potent angiostimulatory molecules and their expression has been demonstrated in many solid tumors, including ovarian cancer.VEGF and IL-8 concentrations were measured by ELISA test (HumanVEGF,IL-8). Bioassay ELISA/ US Biological / USA).The median VEGF and IL-8 levels were significantly higher in the sera of ovarian cancer patients than in those with benign tumors and in healthy controls.Pretreatment VEGF and IL-8 serum levels might be regarded as an additional tool in the differentiation …

Whole Genome Capture Of Vector-Borne Pathogens From Mixed Dna Samples: A Case Study Of Borrelia Burgdorferi, Giovanna Carpi, Katharine S. Walter, Stephen J. Bent, Anne Gatewood Hoen, Maria Diuk-Wasser, Adalgisa Caccone

Dartmouth Scholarship

Background:

Rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. However, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen DNA.

Results:

We addressed this challenge by using custom probes for multiplexed hybrid capture to enrich for and sequence 30 Borrelia burgdorferi genomes from field samples of its arthropod vector. Hybrid …

Regulating Innovation, William W. Fisher Iii

University of Chicago Law Review Online

No abstract provided.

Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major, Justin Daniel Theodore Lange

Theses and Dissertations

The eukaryotic parasite Leishmania is the causative agent of the disease leishmaniasis. L. major is the most common of 21 species that causes visceral leishmaniasis in humans, and 30 that cause the same disease in other mammals. Visceral leishmaniasis causes fever, weight loss, and over a short amount of time, multiple organ failure, and has a 100% mortality rate within 2 years. This makes it the second largest parasitic killer in the world behind malaria. Over 90% of the worldâ??s cases of visceral leishmaniasis have been reported in underdeveloped countries of India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil, with 500,000 …

Analysis Of The Microbial Community Along Three Sites Of The Rio Grande By Denaturing Gradient Gel Electrophoresis, Rebeca Imelda Castro

Theses and Dissertations

ABSTRACT Analysis of the Microbial Community of Three Sites Along the Rio Grande by Denaturing Gradient Gel Electrophoresis (May 2014) Rebeca Imelda Castro, B. A., Texas A & M International University; Chair of Committee: Dr. Monica Mendez In the last decades, the increase in population growth and differences in enforcement regulations on both sides of the Rio Grande may have affected the bacterial composition as a result of effluent discharges, industrial waste, raw sewage outfalls, and agricultural runoff. The purpose of this study was to compare structural differences in the microbial communities of the Rio Grande-Rio Bravo waters based on …

Abq Free Press, June 3, 2015, Abq Free Press

ABQ Free Press

No abstract provided.

Volume 52, Number 42: June 03, 2015, University Of North Dakota

University Letter Archive

No abstract provided.

Respiratory Function Amongst Asymptomatic Hiv Positive And Hiv Negative Clients At Aga Khan University Hospital, Nairobi, Noah Kipkemei Murbiy

Master of Medicine in Internal Medicine

Background: Spirometry is used to asses respiratory function abnormalities. This is usually in reference to a validated normal range unique to a particular gender, race, age, weight and height. Majority of persons are usually asymptomatic until the expected FEV1 has decreased by 50%. Early intervention on the abnormalities even in this asymptomatic group has been shown to retard the rate of pulmonary deterioration. An unpublished audit at the Aga Khan University Hospital, Nairobi, revealed that majority of newly diagnosed HIV positive persons were admitted at the Critical Care Units with a pulmonary cause which later resulted in poor outcomes. This …

Wofford Today Summer 2015, Wofford College. Office Of Marketing And Communications

Wofford Today

No abstract provided.

Erythema Migrans, Robert B. Nadelman

NYMC Faculty Publications

Erythema migrans (EM) is the most common objective manifestation of Borrelia burgdorferi infection. Systemic symptoms are usually present. Most patients do not recall a preceding tick bite. Despite a characteristic appearance, EM is not pathognomonic for Lyme disease and must be distinguished from other similar appearing skin lesions. EM is a clinical diagnosis; serologic and PCR assays are unnecessary. Leukopenia and thrombocytopenia are indicative of either an alternative diagnosis, or coinfection with another tick-borne pathogen. When EM is promptly treated with appropriate antimicrobial agents, the prognosis is excellent. Persons in endemic areas should take measures to prevent tick bites.

Evaluation Of A Real-Time Reverse Transcription-Pcr Assay For Detection Of Enterovirus D68 In Clinical Samples From An Outbreak In New York State In 2014, Jian Zhuge, Eric Vail, Jeffrey L. Bush, Lauren Singelakis, Weihua Huang, Sheila M. Nolan, Janet P. Haas, Helen Engel, Millicent Della Posta, Esther C. Yoon, John T. Fallon, Guiqing Wang

NYMC Faculty Publications

An outbreak of severe respiratory illness associated with enterovirus D68 (EV-D68) infection was reported in mid-August 2014 in the United States. In this study, we evaluated the diagnostic utility of an EV-D68-specific real-time reverse transcription-PCR (rRT-PCR) that was recently developed by the Centers for Disease Control and Prevention in clinical samples. Nasopharyngeal (NP) swab specimens from patients in a recent outbreak of respiratory illness in the lower Hudson Valley, New York State, were collected and examined for the presence of human rhinovirus or enterovirus using the FilmArray Respiratory Panel (RP) assay. Samples positive by RP were assessed using EV-D68 rRT-PCR, …

A Computer-Based Automated Reminder Increases The Percentage Of Urinary Catheters Justified By An Order And Increases Urinary Catheter Discontinuation Orders, Rebecca V. Nadelman, Daniel A. Nadelman, Marisa A. Montecalvo

NYMC Faculty Publications

Use of an automated reminder for an order to continue or to discontinue a urinary catheter resulted in a significant increase in the percentage of urinary catheters justified by an order and the percentage of urinary catheter discontinuation orders increased. This is an essential first step toward reducing inappropriate urinary catheter use.

Questionable Validity Of The Catheter-Associated Urinary Tract Infection Metric Used For Value-Based Purchasing, Lindsay E. Calderon, Kevin T. Kavanagh, Mara K. Rice

Biological Sciences Faculty and Staff Research

Catheter-associated urinary tract infections (CAUTIs) occur in 290,000 US hospital patients annually, with an estimated cost of $290 million. Two different measurement systems are being used to track the US health care system's performance in lowering the rate of CAUTIs. Since 2010, the Agency for Healthcare Research and Quality (AHRQ) metric has shown a 28.2% decrease in CAUTI, whereas the Centers for Disease Control and Prevention metric has shown a 3%-6% increase in CAUTI since 2009. Differences in data acquisition and the definition of the denominator may explain this discrepancy. The AHRQ metric analyzes chart-audited data and reflects both catheter …

Daily Activity Patterns Of 2,316 Men And Women From Five Countries Differing In Socioeconomic Development, Mamane Sani, Roberto Refinetti

Psychological Sciences Faculty Publications and Presentations

Daily rhythmicity in the locomotor activity of laboratory animals has been studied in great detail for many decades, but the daily pattern of locomotor activity has not received as much attention in humans. We collected waist-worn accelerometer data from more than 2,000 individuals from five countries differing in socioeconomic development and conducted a detailed analysis of human locomotor activity. Body mass index was computed from height and weight. Individual activity records lasting 7 days were subjected to cosinor analysis to determine the parameters of the daily activity rhythm: mesor (mean level), amplitude (half the range of excursion), acrophase (time of …

What’S The Value Of Teaching The Liberal Arts? Ask Adam Smith, Louis D. Johnston

Economics Faculty Publications

No abstract provided.

Evolution And Otitis Media: A Review, And A Model To Explain High Prevalence In Indigenous Populations, Mahmood F. Bhutta

Human Biology Open Access Pre-Prints

Inflammation of the middle ear (otitis media) comprises a group of disorders that are highly prevalent in childhood, and indeed are amongst the most common disorders of childhood. Otitis media is also heritable, and has effects on fecundity. This means that otitis media is subject to evolution, yet the evolutionary selection forces that may determine susceptibility to otitis media have never been adequately explored.

Here I undertake a critical analysis of evolutionary forces that may determine susceptibility to middle ear inflammation. These forces include those determining function of the middle ear, those affecting host immunity, and those affecting colonization by, …

Update And Commentary On Four Emerging Tick-Borne Infections: Ehrlichia Muris-Like Agent, Borrelia Miyamotoi, Deer Tick Virus, Heartland Virus, And Whether Ticks Play A Role In Transmission Of Bartonella Henselae, Gary P. Wormser, Bobbi Pritt

NYMC Faculty Publications

Emerging tick-borne infections continue to be observed in the United States and elsewhere. Current information on the epidemiology, clinical and laboratory features, and treatment of infections due to Ehrlichia muris-like agent, deer tick virus, Borrelia miyamotoi sensu lato, and Heartland virus was provided and critically reviewed. More research is needed to define the incidence and to understand the clinical and the laboratory features of these infections. There is also a growing need for the development of sensitive and specific serologic and molecular assays for these infections that are easily accessible to clinicians.

Comparison Of A Quantitative Pcr Assay With Peripheral Blood Smear Examination For Detection And Quantitation Of Babesia Microti Infection In Humans, Guiqing Wang, Patrick Villafuerte, Jian Zhuge, Paul Visintainer, Gary P. Wormser

NYMC Faculty Publications

Using a real-time quantitative PCR (qPCR), we determined the number of DNA copies/mL of blood of a Babesia microti gene in infected patients. Thirty-six patients (whose median age was 62.5years and 75.0% were male) with at least 1 qPCR-positive blood sample were included in this analysis, including 16 with serial blood samples. Based on testing of serial blood samples, it could be demonstrated that the smear became negative while the qPCR remained positive. A moderate to strong correlation was found between the DNA copy number and the number of infected erythrocytes per milliliter of blood (Pearson's r=0.68, P<0.001). Based on limited data, the DNA copy number fell by a mean of 4.1-12.9% per day on active treatment and by 3.5-7.1% per day off therapy. qPCR methodology may permit systematic evaluations of the relative efficacy of various antiparasitic drug regimens and other therapeutic modalities, although a limitation of such testing is that DNA detection per se does not establish the presence of viable parasites.

The 24th Annual Research Conference Abstract Booklet, University Of Gondar, Ethiopia

University of Gondar Research Conferences

The 25th Annual Staff-Student Research Conference of the University of Gondar will be held on June 19 and 20, 2015 at the Science Amba Auditorium. This year's conference is special in that the year marks the Silver Jubilee of the Annual Staff and Student Research Conference. Drawing on the experiences we have accumulated for the past 25 years, we vow to strive to realize the development and transformation of the country through research and community services.

Staff, postgraduate and senior undergraduate students of the University, invited guests, and speakers will participate in the conference. The annual conference of the University …

Penile Microbiota And Female Partner Bacterial Vaginosis In Rakai, Uganda, Cindy M. Liu, Bruce A. Hungate, Aaron A.R. Tobian, Jacques Ravel, Lance B. Price, +8 Additional Authors

Environmental and Occupational Health Faculty Publications

Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community …

Brief Of Amici Curiae Human Rights Organizations In Support Of Plaintiffs-Appellants, Georges V. United Nations, Docket No. 15-00455 (Second Circuit 2015), William Aceves, Baher Azmy, Sarah Dávila-Ruhaak

Court Documents and Proposed Legislation

Amici Curiae consist of twenty-four human rights organizations from the United States and around the world that are committed to the rule of law and respect for fundamental rights, including the essential requirement of accountability for wrongdoing. Amici are deeply concerned that thousands of innocent victims of the 2010 cholera outbreak in Haiti, which is widely acknowledged to have been caused by the United Nations and the United Nations Stabilization Mission in Haiti (“MINUSTAH”), have received no redress for their suffering and injuries. This cholera epidemic compounded the profound suffering already experienced by the Haitian people as a result of …

Human Immunodeficiency Virus (Hiv) In Washington, D.C.: Prevalence Of Antiretroviral Resistance In Treatment Naïve Patients From 2007 To 2010, Matthew J. Swierzbinski, Virginia L. Kan, David M. Parenti

Medicine Faculty Publications

HIV treatment has been greatly impacted by transmitted resistance to antiretrovirals (ARV). Several studies have documented resistance in naïve individuals and estimates of transmitted drug resistance mutations range from <5% to as high as 25%. Washington, D.C. has one of the highest human immunodeficiency virus (HIV) prevalence rates in the United States (3.2% in 2009), but local data regarding the frequency of major mutations and antiretroviral (ARV) resistance has been limited. Medical records of HIV positive, ARV-naïve adults at two facilities in Washington, D.C., The George Washington University Medical Center and the Veterans Affairs Medical Center, were retrospectively analyzed in subjects who had genotypic resistance testing from 2007 to 2010. Of 407 ARV-naïve patients, at least one transmitted drug resistance mutation was detected in 17% of our patients, with non-nucleoside reverse transcriptase (NNRTI) mutations observed in 15%. Among patients with at least one reverse transcriptase (RT) or major protease region (Pr) resistance mutation, 85% had resistance against a single ARV class. Dual and triple class resistance mutations were seen in 8 patients (2%) and 3 patients (0.7%), respectively. Most of the multiple class resistance was seen in 2010. A gradual increase in NNRTI resistance was noted during 2008 to 2010. Our prevalence of transmitted RT, major Pr mutations (17.4%) and ARV resistance (8.6%) were high but similar to rates reported by others within the United States. Given the high HIV prevalence in the District of Columbia, this has important implications for treatment of these ARV-naïve patients.

Genome-Wide Association Study And Admixture Mapping Reveal New Loci Associated With Total Ige Levels In Latinos, Maria Pino-Yanes, Christopher R. Gignoux, Joshua M. Galanter, Albert M. Levin, Catarina D. Campbell, Celeste Eng, Scott Huntsman, Katherine K. Nishimura, Pierre-Antoine Gourraud, Kiana Mohajeri, Brian O'Roak, Donglei Hu, Rasika A. Mathias, Elizabeth A. Nguyen, Lindsey A. Roth, Badri Padhukasahasram, Andres Moreno-Estrada, Karla Sandoval, Cheryl A. Winkler, Fred Lurmann, Adam Davis, Harold J. Farber, Kelley Meade, Pedro C. Avila, Denise Serebrisky, Rocio Chapela, Jean G. Ford, Michael A. Lenoir, Shannon M. Thyne, Emerita Brigino-Buenaventura, Luisa N. Borrell, William Rodriguez-Cintron, Saunak Sen, Rajesh Kumar, Jose R. Rodriguez-Santana, Carlos D. Bustamante, Fernando D. Martinez, Benjamin A. Raby, Scott T. Weiss, Dan L. Nicolae, Carole Ober, Deborah A. Meyers, Eugene R. Bleecker, Steven J. Mack, Ryan D. Hernandez, Evan E. Eichler, Kathleen C. Barnes, Keoki L. Williams, Dara G. Torgerson, Esteban G. Burchard

Center for Health Policy and Health Services Research Articles

BACKGROUND: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.

OBJECTIVE: We sought to identify genetic variants associated with IgE levels in Latinos.

METHODS: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.

RESULTS: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of …

A Stage-Structured Two Species Competition Mathematical Model Under The Effect Of Disease, Manju Agarwal, Vinay Verma

Applications and Applied Mathematics: An International Journal (AAM)

In this paper we study the dynamics of two competing species model; one of this competing species is stage structured and the disease spreads only in the other competing specie. In order to keep the model simple, we present it under the strong assumption that the disease can not cross the species barrier. Dynamical behaviors such as positivity, boundedness, stability, bifurcation and persistence of the model are studied analytically using the theory of differential equations. Computer simulations are carried out to substantiate the analytical findings. It is noted that c the loss rate of the population, T the maturation time …

Computed Tomography-Guided Biopsy For Potts Disease: An Institutional Experience From An Endemic Developing Country, Muhammad Waqas, Mohsin Qadeer, Faizuddin Faiz, Mohammad Ali Alvi, Muhammad Ehsan Bari

Section of Neurosurgery

Study design: A retrospective chart review.
Purpose: In endemic resource poor countries like Pakistan, most patients are diagnosed and treated for Potts disease on clinical and radiological grounds without a routine biopsy. The purpose of this study was to evaluate the use and effect of computed tomography (CT)-guided biopsy in the management of Potts disease since the technique is becoming increasingly available.
Overview of literature: CT-guided biopsy of spinal lesions is routinely performed. Literature on the utility of the technique in endemic resource poor countries is little.
Methods: This study was conducted at the Neurosurgery section of Aga Khan University …