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2012

Humans

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Articles 1 - 30 of 509

Full-Text Articles in Medicine and Health Sciences

Potentials And Limitations Of Real-Time Elastography For Prostate Cancer Detection: A Whole-Mount Step Section Analysis., Daniel Junker, Georg Schäfer, Friedrich Aigner, Peter Schullian, Leo Pallwein-Prettner, Jasmin Bektic, Wolfgang Horninger, Ethan J Halpern, Ferdinand Frauscher Dec 2012

Potentials And Limitations Of Real-Time Elastography For Prostate Cancer Detection: A Whole-Mount Step Section Analysis., Daniel Junker, Georg Schäfer, Friedrich Aigner, Peter Schullian, Leo Pallwein-Prettner, Jasmin Bektic, Wolfgang Horninger, Ethan J Halpern, Ferdinand Frauscher

Department of Radiology Faculty Papers

OBJECTIVES: To evaluate prostate cancer (PCa) detection rates of real-time elastography (RTE) in dependence of tumor size, tumor volume, localization and histological type.

MATERIALS AND METHODS: Thirdy-nine patients with biopsy proven PCa underwent RTE before radical prostatectomy (RPE) to assess prostate tissue elasticity, and hard lesions were considered suspicious for PCa. After RPE, the prostates were prepared as whole-mount step sections and were compared with imaging findings for analyzing PCa detection rates.

RESULTS: RTE detected 6/62 cancer lesions with a maximum diameter of 0-5 mm (9.7%), 10/37 with a maximum diameter of 6-10 mm (27%), 24/34 with a maximum diameter …


Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella Dec 2012

Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella

Dartmouth Scholarship

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from …


On The Interplay Of Telomeres, Nevi And The Risk Of Melanoma, Clara Bodelon, Ruth M. Pfeiffer, Valentina Bollati, Julien Debbache, Donato Calista, Paola Ghiorzo, Maria Concetta Fargnoli, Giovanna Bianchi-Scarra, Ketty Peris, Mirjam Hoxha, Amy Hutchinson, Laura Burke, Shenying Fang, Margaret A. Tucker, Alisa M. Goldstein, Jeffrey E. Lee, Qingyi Wei, Sharon A. Savage, Xiaohong R. Yang, Christopher Amos, Maria Teresa Landi Dec 2012

On The Interplay Of Telomeres, Nevi And The Risk Of Melanoma, Clara Bodelon, Ruth M. Pfeiffer, Valentina Bollati, Julien Debbache, Donato Calista, Paola Ghiorzo, Maria Concetta Fargnoli, Giovanna Bianchi-Scarra, Ketty Peris, Mirjam Hoxha, Amy Hutchinson, Laura Burke, Shenying Fang, Margaret A. Tucker, Alisa M. Goldstein, Jeffrey E. Lee, Qingyi Wei, Sharon A. Savage, Xiaohong R. Yang, Christopher Amos, Maria Teresa Landi

Dartmouth Scholarship

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or …


Hyperosmolar Therapy For Raised Intracranial Pressure., Ethan A Benardete Dec 2012

Hyperosmolar Therapy For Raised Intracranial Pressure., Ethan A Benardete

Department of Neurosurgery Faculty Papers

No abstract provided.


Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini Dec 2012

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …


Evaluating Changes In Radiation Treatment Volumes From Post-Operative To Same-Day Planning Mri In High-Grade Gliomas., Colin E Champ, Joshua Siglin, Mark V Mishra, Xinglei Shen, Maria Werner-Wasik, David W Andrews, Sonal U Mayekar, Haisong Liu, Wenyin Shi Dec 2012

Evaluating Changes In Radiation Treatment Volumes From Post-Operative To Same-Day Planning Mri In High-Grade Gliomas., Colin E Champ, Joshua Siglin, Mark V Mishra, Xinglei Shen, Maria Werner-Wasik, David W Andrews, Sonal U Mayekar, Haisong Liu, Wenyin Shi

Department of Radiation Oncology Faculty Papers

BACKGROUND: Adjuvant radiation therapy (RT) with temozolomide (TMZ) is standard of care for high grade gliomas (HGG) patients. RT is commonly started 3 to 5 weeks after surgery. The deformation of the tumor bed and brain from surgery to RT is poorly studied. This study examined the magnitude of volume change in the postoperative tumor bed and the potential impact of RT planning.

METHOD AND MATERIALS: This study includes 24 patients with HGG who underwent craniotomy and adjuvant RT with TMZ at our institution. All patients had immediate postoperative MRI and repeat MRI during the day of RT simulation. Gross …


Successful Identification Of Pathogens By Polymerase Chain Reaction (Pcr)-Based Electron Spray Ionization Time-Of-Flight Mass Spectrometry (Esi-Tof-Ms) In Culture-Negative Periprosthetic Joint Infection., Christina L Jacovides, Rachael Kreft, Bahar Adeli, Bryan Hozack, Garth D Ehrlich, Javad Parvizi Dec 2012

Successful Identification Of Pathogens By Polymerase Chain Reaction (Pcr)-Based Electron Spray Ionization Time-Of-Flight Mass Spectrometry (Esi-Tof-Ms) In Culture-Negative Periprosthetic Joint Infection., Christina L Jacovides, Rachael Kreft, Bahar Adeli, Bryan Hozack, Garth D Ehrlich, Javad Parvizi

Rothman Institute Faculty Papers

BACKGROUND: The diagnosis of periprosthetic joint infection poses many challenges, one of which is the difficulty of isolating the infecting organism. Recently, a sophisticated modality (the Ibis Biosciences T5000 biosensor system) has been introduced that uses pan-domain primers in a series of polymerase chain reactions (PCRs) to identify and speciate essentially all bacteria and fungi as well as to identify key antibiotic resistance genes. We investigated the role of the Ibis in identifying infecting organisms in cases of known and suspected periprosthetic joint infection.

METHODS: Synovial fluid specimens were collected prospectively from eighty-two patients undergoing eighty-seven arthroplasty procedures (sixty-five knee …


Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson Dec 2012

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …


Treatment Of Klebsiella Pneumoniae Carbapenemase (Kpc) Infections: A Review Of Published Case Series And Case Reports, Grace C. Lee, David S. Burgess Dec 2012

Treatment Of Klebsiella Pneumoniae Carbapenemase (Kpc) Infections: A Review Of Published Case Series And Case Reports, Grace C. Lee, David S. Burgess

Pharmacy Practice and Science Faculty Publications

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment …


Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang Dec 2012

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …


Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007-2010, Earl S. Ford, Anne G. Wheaton, David M. Mannino, Letitia Presley-Cantrell, Chaoyang Li, Janet B. Croft Dec 2012

Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007-2010, Earl S. Ford, Anne G. Wheaton, David M. Mannino, Letitia Presley-Cantrell, Chaoyang Li, Janet B. Croft

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear. Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.

METHODS: We used data from adults aged 20-79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test. The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.

RESULTS: Among 7249 participants, 80.9% had …


Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown Dec 2012

Targeted Mutation Of Mouse Skeletal Muscle Sodium Channel Produces Myotonia And Potassium-Sensitive Weakness, Lawrence Hayward, Joanna Kim, Ming-Yang Lee, Hongru Zhou, Ji Kim, Kumudini Misra, Mohammad Salajegheh, Fen-Fen Wu, Shinji Matsuda, Valerie Reid, Didier Cros, Eric Hoffman, Jean-Marc Renaud, Stephen Cannon, Robert Brown

Dr Robert Brown

Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness …


Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader Dec 2012

Loss-Of-Function Variants In Endothelial Lipase Are A Cause Of Elevated Hdl Cholesterol In Humans, Andrew Edmondson, Robert Brown, Sekar Kathiresan, L. Cupples, Serkalem Demissie, Alisa Manning, Majken Jensen, Eric Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet Khetarpal, Megan Wolfe, Stephanie Derohannessian, Mingyao Li, Muredach Reilly, Jens Aberle, David Evans, Robert Hegele, Daniel Rader

Dr Robert Brown

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated …


Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown Dec 2012

Decreased Metallation And Activity In Subsets Of Mutant Superoxide Dismutases Associated With Familial Amyotrophic Lateral Sclerosis, Lawrence Hayward, Jorge Rodriguez, Ji Kim, Ashutosh Tiwari, Joy Goto, Diane Cabelli, Joan Valentine, Robert Brown

Dr Robert Brown

Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause approximately 2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a …


Influence Of Body Mass Index And Antibiotic Dose On The Risk Of Surgical Site Infections In Pediatric Clean Orthopedic Surgery., Jeffrey J Cies, Shannon Chan, Jobayer Hossain, B Randall Brenn, M Cecilia Di Pentima Dec 2012

Influence Of Body Mass Index And Antibiotic Dose On The Risk Of Surgical Site Infections In Pediatric Clean Orthopedic Surgery., Jeffrey J Cies, Shannon Chan, Jobayer Hossain, B Randall Brenn, M Cecilia Di Pentima

Department of Anesthesiology Faculty Papers

OBJECTIVE: To evaluate body mass index (BMI) and antimicrobial dose as risk factors for surgical site infections in pediatric patients.

PATIENTS AND METHODS: Children between 2 and 19 years of age undergoing clean orthopedic procedures and receiving at least one dose of perioperative antibiotics (cefazolin, vancomycin, or clindamycin) were studied. The retrospective case-controlled study was conducted at the Alfred I. duPont Hospital for Children, a 180-bed tertiary-care academic pediatric hospital in Wilmington, DE. Data were collected from January 1, 2002, to December 31, 2005.

RESULTS: Underweight children had a higher risk for SSIs than overweight and normal-weight children. American Society …


Transforming The Healthcare Response To Intimate Partner Violence And Taking Best Practices To Scale, Michele R. Decker, Shannon Frattaroli, Brigid Mccaw, Ann L. Coker, Elizabeth Miller, Phyllis Sharps, Wendy G. Lane, Mahua Mandal, Kelli Hirsch, Donna M. Strobino, Wendy L. Bennett, Jacquelyn Campbell, Andrea Gielen Dec 2012

Transforming The Healthcare Response To Intimate Partner Violence And Taking Best Practices To Scale, Michele R. Decker, Shannon Frattaroli, Brigid Mccaw, Ann L. Coker, Elizabeth Miller, Phyllis Sharps, Wendy G. Lane, Mahua Mandal, Kelli Hirsch, Donna M. Strobino, Wendy L. Bennett, Jacquelyn Campbell, Andrea Gielen

CRVAW Faculty Journal Articles

BACKGROUND: Intimate partner violence (IPV) is prevalent among adolescent and adult women, with significant physical, sexual, and mental health consequences. In 2011, the Institute of Medicine's Clinical Preventive Services for Women consensus report recommended universal screening for violence as a component of women's preventive services; this policy has been adopted by the Health Resources and Services Administration (HRSA). These policy developments require that effective clinic-based interventions be identified, easily implemented, and taken to scale.

METHODS: To foster dialogue about implementing effective interventions, we convened a symposium entitled "Responding to Violence Against Women: Emerging Evidence, Implementation Science, and Innovative Interventions," on …


Parenteral Nutrition Additive Shortages: The Short-Term, Long-Term And Potential Epigenetic Implications In Premature And Hospitalized Infants., Corrine K. Hanson, Melissa Thoene, Julie Wagner, Dean Collier, Kassandra Lecci, Ann Anderson-Berry Dec 2012

Parenteral Nutrition Additive Shortages: The Short-Term, Long-Term And Potential Epigenetic Implications In Premature And Hospitalized Infants., Corrine K. Hanson, Melissa Thoene, Julie Wagner, Dean Collier, Kassandra Lecci, Ann Anderson-Berry

Journal Articles: Medical Nutrition

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages …


Evaluation Of Very High- And Very Low-Dose Intravitreal Aflibercept In Patients With Neovascular Age-Related Macular Degeneration., Quan Dong Nguyen, Peter A. Campochiaro, Syed Mahmood Shah, David J. Browning, Henry L. Hudson, Peter L. Sonkin, Seenu M. Hariprasad, Peter K. Kaiser, Jason Slakter, Julia A. Haller, Diana V. Do, William Mieler, Karen Chu, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Jesse Cedarbaum, Clear-It 1 Investigators Dec 2012

Evaluation Of Very High- And Very Low-Dose Intravitreal Aflibercept In Patients With Neovascular Age-Related Macular Degeneration., Quan Dong Nguyen, Peter A. Campochiaro, Syed Mahmood Shah, David J. Browning, Henry L. Hudson, Peter L. Sonkin, Seenu M. Hariprasad, Peter K. Kaiser, Jason Slakter, Julia A. Haller, Diana V. Do, William Mieler, Karen Chu, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Jesse Cedarbaum, Clear-It 1 Investigators

Journal Articles: Ophthalmology

PURPOSE: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD).

METHODS: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, …


Gsk3Β Inhibition Blocks Melanoma Cell/Host Interactions By Downregulating N-Cadherin Expression And Decreasing Fak Phosphorylation., Jobin K John, Kim H T Paraiso, Vito W Rebecca, Liliana P Cantini, Ethan V Abel, Nicholas Pagano, Eric Meggers, Rahel Mathew, Clemens Krepler, Victoria Izumi, Bin Fang, John M Koomen, Jane L Messina, Meenhard Herlyn, Keiran S M Smalley Dec 2012

Gsk3Β Inhibition Blocks Melanoma Cell/Host Interactions By Downregulating N-Cadherin Expression And Decreasing Fak Phosphorylation., Jobin K John, Kim H T Paraiso, Vito W Rebecca, Liliana P Cantini, Ethan V Abel, Nicholas Pagano, Eric Meggers, Rahel Mathew, Clemens Krepler, Victoria Izumi, Bin Fang, John M Koomen, Jane L Messina, Meenhard Herlyn, Keiran S M Smalley

Department of Cancer Biology Faculty Papers

This study addresses the role of glycogen synthase kinase (GSK)-3β signaling in the tumorigenic behavior of melanoma. Immunohistochemical staining revealed GSK3β to be focally expressed in the invasive portions of 12 and 33% of primary and metastatic melanomas, respectively. GSK3 inhibitors and small interfering RNA (siRNA) knockdown of GSK3β were found to inhibit the motile behavior of melanoma cells in scratch wound, three-dimensional collagen-implanted spheroid, and modified Boyden chamber assays. Functionally, inhibition of GSK3β signaling was found to suppress N-cadherin expression at the messenger RNA and protein levels, and was associated with decreased expression of the transcription factor Slug. Pharmacological …


Effect Of Voxel Size On The Accuracy Of 3d Reconstructions With Cone Beam Ct., Delphine Maret, Norbert Telmon, Ove A. Peters, B. Lepage, J. Treil, J. M. Inglèse, A. Peyre, Jean-Luc Kahn, Michel Sixou Dec 2012

Effect Of Voxel Size On The Accuracy Of 3d Reconstructions With Cone Beam Ct., Delphine Maret, Norbert Telmon, Ove A. Peters, B. Lepage, J. Treil, J. M. Inglèse, A. Peyre, Jean-Luc Kahn, Michel Sixou

All Dugoni School of Dentistry Faculty Articles

OBJECTIVES: The various types of cone beam CT (CBCT) differ in several technical characteristics, notably their spatial resolution, which is defined by the acquisition voxel size. However, data are still lacking on the effects of voxel size on the metric accuracy of three-dimensional (3D) reconstructions. This study was designed to assess the effect of isotropic voxel size on the 3D reconstruction accuracy and reproducibility of CBCT data.

METHODS: The study sample comprised 70 teeth (from the Institut d'Anatomie Normale, Strasbourg, France). The teeth were scanned with a KODAK 9500 3D® CBCT (Carestream Health, Inc., Marne-la-Vallée, France), which has two voxel …


Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung Dec 2012

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …


Treatment Of Steroid-Induced Elevated Intraocular Pressure With Anecortave Acetate: A Randomized Clinical Trial., Ingeborg Stalmans, David G. Callanan, Monte S. Dirks, Marlene R. Moster, Alan L. Robin, Joachim Van Calster, Sally A. Scheib, Jaime E. Dickerson, Theresa A. Landry, Michael V. W. Bergamini Dec 2012

Treatment Of Steroid-Induced Elevated Intraocular Pressure With Anecortave Acetate: A Randomized Clinical Trial., Ingeborg Stalmans, David G. Callanan, Monte S. Dirks, Marlene R. Moster, Alan L. Robin, Joachim Van Calster, Sally A. Scheib, Jaime E. Dickerson, Theresa A. Landry, Michael V. W. Bergamini

Wills Eye Hospital Papers

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy.

METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of …


Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue Dec 2012

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations & Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …


Changes In Serum Interleukin-33 Concentration Before And After Treatment With Pegylated Interferon Alfa-2a Plus Ribavirin In Patients With Chronic Hepatitis C Genotype 1b Infection., Bruno Cacopardo, Marilia Rita Pinzone, Filippo Palermo, Giuseppe Nunnari Dec 2012

Changes In Serum Interleukin-33 Concentration Before And After Treatment With Pegylated Interferon Alfa-2a Plus Ribavirin In Patients With Chronic Hepatitis C Genotype 1b Infection., Bruno Cacopardo, Marilia Rita Pinzone, Filippo Palermo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: IL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis.

OBJECTIVES: To evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin.

PATIENTS AND METHODS: 60 patients with chronic hepatitis C (CHC) and 65 …


Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele Nov 2012

Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × …


Slides: Colorado Law: Protecting Water Quantity And Quality, Alan E. Curtis Nov 2012

Slides: Colorado Law: Protecting Water Quantity And Quality, Alan E. Curtis

Monitoring and Protecting Groundwater During Oil and Gas Development (November 26)

Presenter: Alan E. Curtis, White & Jankowski, LLP

23 slides


Joint Effect Of Genetic And Lifestyle Risk Factors On Type 2 Diabetes Risk Among Chinese Men And Women, Raquel Villegas, Ryan Delahanty, Yu-Tang Gao, Jirong Long, Scott M. Williams, Yong-Bing Xiang, Hui Cai, Hong-Lan Li, Frank Hu, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu Nov 2012

Joint Effect Of Genetic And Lifestyle Risk Factors On Type 2 Diabetes Risk Among Chinese Men And Women, Raquel Villegas, Ryan Delahanty, Yu-Tang Gao, Jirong Long, Scott M. Williams, Yong-Bing Xiang, Hui Cai, Hong-Lan Li, Frank Hu, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu

Dartmouth Scholarship

More than 40 genetic susceptibility loci have been reported for type 2 diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) …


Risk Factors For Wound Complications After Ankle Fracture Surgery., Adam G Miller, Andrew Margules, Steven M Raikin Nov 2012

Risk Factors For Wound Complications After Ankle Fracture Surgery., Adam G Miller, Andrew Margules, Steven M Raikin

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The overall rate of complications after ankle fracture fixation varies between 5% and 40% depending on the population investigated, and wound complications have been reported to occur in 1.4% to 18.8% of patients. Large studies have focused on complications in terms of readmission, but few studies have examined risk factors for wound-related issues in the outpatient setting in a large number of patients. A review was performed to identify risk factors for wound complications tracked in the hospital and outpatient setting.

METHODS: Four hundred and seventy-eight patients underwent open reduction and internal fixation of an ankle fracture between 2003 …


Practice Effects In A Longitudinal, Multi-Center Alzheimer's Disease Prevention Clinical Trial, Erin L. Abner, Brandon C. Dennis, Melissa J. Mathews, Marta S. Mendiondo, Allison Caban-Holt, Richard J. Kryscio, Frederick A. Schmitt, John J. Crowley Nov 2012

Practice Effects In A Longitudinal, Multi-Center Alzheimer's Disease Prevention Clinical Trial, Erin L. Abner, Brandon C. Dennis, Melissa J. Mathews, Marta S. Mendiondo, Allison Caban-Holt, Richard J. Kryscio, Frederick A. Schmitt, John J. Crowley

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS).

METHODS: The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less …


Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk Nov 2012

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …