Medicine and Health Sciences Commons^™

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, …

Transforming Growth Factor Alpha (Tgfα) Regulates Granulosa Cell Tumor (Gct) Cell Proliferation And Migration Through Activation Of Multiple Pathways., Cheng Wang, Xiangmin Lv, Chao Jiang, Crystal M. Cordes, Lan Fu, Subodh M. Lele, John S. Davis

Journal Articles: Obstetrics & Gynecology

Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular …

Breast Cancer Incidence In Black And White Women Stratified By Estrogen And Progesterone Receptor Statuses., Michael X. Gleason, Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: There is increasing evidence that breast cancer is a heterogeneous disease presented by different phenotypes and that white women have a higher breast cancer incidence rate, whereas black women have a higher mortality rate. It is also well known that white women have lower incidence rates than black women until approximately age 40, when rate curves cross over and white women have higher rates. The goal of this study was to validate the risk of white and black women to breast cancer phenotypes, stratified by statuses of the estrogen (ER) and progesterone (PR) receptors.

METHODOLOGY/PRINCIPAL FINDINGS: SEER17 data were …

Low Levels Of Β-Lactam Antibiotics Induce Extracellular Dna Release And Biofilm Formation In Staphylococcus Aureus., Jeffrey B. Kaplan, Era A. Izano, Prerna Gopal, Michael T. Karwacki, Sangho Kim, Jeffrey L. Bose, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

UNLABELLED: Subminimal inhibitory concentrations of antibiotics have been shown to induce bacterial biofilm formation. Few studies have investigated antibiotic-induced biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal was to measure S. aureus biofilm formation in the presence of low levels of β-lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added to cultures at concentrations ranging from 0× to 1× MIC. Biofilm formation was measured in 96-well microtiter plates using a crystal violet binding assay. Autoaggregation was measured using a visual test tube …

Inter-Study Reproducibility Of Cardiovascular Magnetic Resonance Myocardial Feature Tracking., Geraint Morton, Andreas Schuster, Roy Jogiya, Shelby Kutty, Philipp Beerbaum, Eike Nagel

Journal Articles: Pediatrics

BACKGROUND: Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a recently described method of post processing routine cine acquisitions which aims to provide quantitative measurements of circumferentially and radially directed ventricular wall strain. Inter-study reproducibility is important for serial assessments however has not been defined for CMR-FT.

METHODS: 16 healthy volunteers were imaged 3 times within a single day. The first examination was performed at 0900 after fasting and was immediately followed by the second. The third, non-fasting scan, was performed at 1400.CMR-FT measures of segmental and global strain parameters were calculated. Left ventricular (LV) circumferential and radial strain were …

Non-Typeable Haemophilus Influenzae Decreases Cilia Beating Via Protein Kinase Cε., Kristina L. Bailey, Tricia D. Levan, Daniel A. Yanov, Jacqueline A. Pavlik, Jane M. Devasure, Joseph H. Sisson, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Haemophilus influenzae infection of the nasal epithelium has long been associated with observations of decreased nasal ciliary beat frequency (CBF) and injury to the ciliated epithelium. Previously, we have reported that several agents that slow CBF also have the effect of activating protein kinase C epsilon (PKCε) activity in bronchial epithelial cells. The subsequent auto-downregulation of PKCε or the direct inhibition of PKCε leads to the specific detachment of the ciliated cells.

METHODS: Primary cultures of ciliated bovine bronchial epithelial cells were exposed to filtered conditioned media supernatants from non-typeable H. influenzae (NTHi) cultures. CBF and motile points were …

Transforming Growth Factor-Β Suppresses Metastasis In A Subset Of Human Colon Carcinoma Cells., Neka A.K. Simms, Ashwani Rajput, Elizabeth A. Sharratt, Melanie Ongchin, Carol A. Teggart, J. Wang, Michael G. Brattain

Journal Articles: Eppley Institute

BACKGROUND: TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling.

METHODS: To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Adjunct Primer For The Use Of National Comprehensive Cancer Network Guidelines For The Surgical Management Of Cutaneous Malignant Melanoma Patients., Edibaldo Silva

Journal Articles: Oncology and Hematology

Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from best practice patterns throughout the country. The study, which analyzed the SEER records of 35,126 stage I to III cutaneous malignant melanoma patients treated from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network (NCCN) therapeutic resection margins occurred in less than 36% of patients. Similarly, considerable variation in the quality of melanoma care in the United States when assessed using 26 quality indicators drawn by a panel of melanoma experts was independently reported. These …

A Heuristic Solution Of The Identifiability Problem Of The Age-Period-Cohort Analysis Of Cancer Occurrence: Lung Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

BACKGROUND: The Age-Period-Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of …

Onset Of Alcohol Or Substance Use Disorders Following Treatment For Adolescent Depression., John Curry, Susan Silva, Paul Rohde, Golda Ginsburg, Betsy Kennard, Christopher Kratochvil, Anne Simons, Jerry Kirchner, Diane May, Taryn Mayes, Norah Feeny, Anne Marie Albano, Sarah Lavanier, Mark Reinecke, Rachel Jacobs, Emily Becker-Weidman, Elizabeth Weller, Graham Emslie, John Walkup, Elizabeth Kastelic, Barbara Burns, Karen Wells, John March

Journal Articles: Psychiatry

OBJECTIVE: This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD).

METHOD: For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original …

Differential Expression Of Metabolic Genes In Tumor And Stromal Components Of Primary And Metastatic Loci In Pancreatic Adenocarcinoma., Nina V. Chaika, Fang Yu, Vinee Purohit, Kamiya Mehla, Audrey J. Lazenby, Dominick J. Dimaio, Judy M. Anderson, Jen Jen Yeh, Keith R. Johnson, Michael A. Hollingsworth, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways …