Medicine and Health Sciences Commons^™

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …

Outcomes With As-Needed Ranibizumab After Initial Monthly Therapy: Long-Term Outcomes Of The Phase Iii Ride And Rise Trials., David S. Boyer, Quan Dong Nguyen, David M. Brown, Karen Basu, Jason S. Ehrlich

Journal Articles: Ophthalmology

PURPOSE: To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

DESIGN: Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

PARTICIPANTS: Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

METHODS: All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by …

Mortality-Related Resource Utilization In The Inpatient Care Of Hypoplastic Left Heart Syndrome., David A. Danford, Quentin Karels, Aparna Kulkarni, Aysha Hussain, Yunbin Xiao, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF).

METHODS: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of …

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …

Primary Sclerosing Epithelioid Fibrosarcoma Of Kidney With Variant Histomorphologic Features: Report Of 2 Cases And Review Of The Literature., Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Oguz Aydin, Julia A. Bridge, Berrin Buyukeren, Fazil Tuncay Aki

Journal Articles: Pathology and Microbiology

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in …

Prognostic Role Of Bnp In Children Undergoing Surgery For Congenital Heart Disease: Analysis Of Prediction Models Incorporating Standard Risk Factors., Massimiliano Cantinotti, Raffaele Giordano, Marco Scalese, Sabrina Molinaro, Francesca Della Pina, Simona Storti, Luigi Arcieri, Bruno Murzi, Marco Marotta, Vitali Pak, Vincenzo Poli, Giorgio Iervasi, Shelby Kutty, Aldo Clerico

Journal Articles: Pediatrics

BACKGROUND: The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery.

METHODS: In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2-35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay >15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score …

The Effect Of Standard Dose Multivitamin Supplementation On Disease Progression In Hiv-Infected Adults Initiating Haart: A Randomized Double Blind Placebo-Controlled Trial In Uganda., David Guwatudde, Molin Wang, Amara E. Ezeamama, Danstan Bagenda, Rachel Kyeyune, Henry Wamani, Yukari C. Manabe, Wafaie W. Fawzi

Journal Articles: Epidemiology

BACKGROUND: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART.

METHODS: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or …

Improving Child Survival Through A District Management Strengthening And Community Empowerment Intervention: Early Implementation Experiences From Uganda., Anne R. Katahoire, Dorcus K. Henriksson, Eric Ssegujja, Peter Waiswa, Florence Ayebare, Danstan Bagenda, Anthony K. Mbonye, Stefan S. Peterson

Journal Articles: Epidemiology

BACKGROUND: The Community and District Empowerment for Scale-up (CODES) project pioneered the implementation of a comprehensive district management and community empowerment intervention in five districts in Uganda. In order to improve effective coverage and quality of child survival interventions CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. This paper presents early implementation experiences in five pilot districts and lessons learnt during the first 2 years of …

Ca2+ Diffusion Through Endoplasmic Reticulum Supports Elevated Intraterminal Ca2+ Levels Needed To Sustain Synaptic Release From Rods In Darkness., Minghui Chen, Matthew J. Van Hook, Wallace B. Thoreson

Journal Articles: Ophthalmology

UNLABELLED: In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow release at non-ribbon release sites triggered by Ca(2+)-induced Ca(2+) release (CICR) from intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that Ca(2+) released into the cytoplasm from terminal endoplasmic reticulum (ER) can be replenished continuously by ions diffusing within the ER from the soma. We measured [Ca(2+)] changes in cytoplasm and ER of rods from Ambystoma tigrinum retina using various dyes. ER [Ca(2+)] changes were measured by loading ER with fluo-5N and then washing dye from the cytoplasm with …

Gonad: Genome-Editing Via Oviductal Nucleic Acids Delivery System: A Novel Microinjection Independent Genome Engineering Method In Mice., Gou Takahashi, Channabasavaiah B. Gurumurthy, Kenta Wada, Hiromi Miura, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in …

Bilateral Papillitis And Unilateral Focal Chorioretinitis As The Presenting Features Of Syphilis., Christy E. Benson, Mohamed K. Soliman, Alexander Knezevic, Daisy D. Xu, Quan D. Nguyen, Diana V V. Do

Journal Articles: Ophthalmology

BACKGROUND: Syphilis is a multisystem bacterial infection caused by Treponema pallidum. The incidence of infection in the United States has risen by more than 75% since the year 2000, when it was at a low of 2.1 per 100,000 people. Ocular involvement may occur in any stage of infection and may present in a variety of ways, with posterior uveitis being the most common manifestation. We report a case of ocular syphilis infection with an unusual presentation of bilateral non-granulomatous panuveitis with papillitis and unilateral focal chorioretinitis.

FINDINGS: This is a retrospective case report with literature review. A 39-year-old Caucasian …

Quantification Of Atrial Dynamics Using Cardiovascular Magnetic Resonance: Inter-Study Reproducibility., Johannes T. Kowallick, Geraint Morton, Pablo Lamata, Roy Jogiya, Shelby Kutty, Gerd Hasenfuß, Joachim Lotz, Eike Nagel, Amedeo Chiribiri, Andreas Schuster

Journal Articles: Cardiology

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers quantification of phasic atrial functions based on volumetric assessment and more recently, on CMR feature tracking (CMR-FT) quantitative strain and strain rate (SR) deformation imaging. Inter-study reproducibility is a key requirement for longitudinal studies but has not been defined for CMR-based quantification of left atrial (LA) and right atrial (RA) dynamics.

METHODS: Long-axis 2- and 4-chamber cine images were acquired at 9:00 (Exam A), 9:30 (Exam B) and 14:00 (Exam C) in 16 healthy volunteers. LA and RA reservoir, conduit and contractile booster pump functions were quantified by volumetric indexes as derived from fractional …

One-Step Generation Of Multiple Transgenic Mouse Lines Using An Improved Pronuclear Injection-Based Targeted Transgenesis (I-Pitt)., Masato Ohtsuka, Hiromi Miura, Keiji Mochida, Michiko Hirose, Ayumi Hasegawa, Atsuo Ogura, Ryuta Mizutani, Minoru Kimura, Ayako Isotani, Masahito Ikawa, Masahiro Sato, Channabasavaiah B. Gurumurthy

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The pronuclear injection (PI) is the simplest and widely used method to generate transgenic (Tg) mice. Unfortunately, PI-based Tg mice show uncertain transgene expression due to random transgene insertion in the genome, usually with multiple copies. Thus, typically at least three or more Tg lines are produced by injecting over 200 zygotes and the best line/s among them are selected through laborious screening steps. Recently, we developed technologies using Cre-loxP system that allow targeted insertion of single-copy transgene into a predetermined locus through PI. We termed the method as PI-based Targeted Transgenesis (PITT). A similar method using PhiC31-attP/B system …

Myocardial Feature Tracking Reduces Observer-Dependence In Low-Dose Dobutamine Stress Cardiovascular Magnetic Resonance., Andreas Schuster, Matthias Paul, Nuno Bettencourt, Shazia T. Hussain, Geraint Morton, Shelby Kutty, Boris Bigalke, Amedeo Chiribiri, Divaka Perera, Eike Nagel, Philipp Beerbaum

Journal Articles: Cardiology

OBJECTIVES: To determine whether quantitative wall motion assessment by CMR myocardial feature tracking (CMR-FT) would reduce the impact of observer experience as compared to visual analysis in patients with ischemic cardiomyopathy (ICM).

METHODS: 15 consecutive patients with ICM referred for assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine images at rest and during low dose dobutamine stress (5 and 10 μg/kg/min of dobutamine). Conventional visual, qualitative analysis was performed independently and blinded by an experienced and an inexperienced reader, followed by post-processing of the same images by CMR-FT to quantify subendocardial and subepicardial circumferential (Eccendo and …

Refractory Angiosarcoma Of The Breast With Vegfr2 Upregulation Successfully Treated With Sunitinib., Edibaldo Silva, Zoran Gatalica, Semir Vranic, Gargi Basu, Sandeep K. Reddy, Andreas Voss

Journal Articles: Surgery

No abstract provided.

Amyloid Precursor-Like Protein 2 (Aplp2) Affects The Actin Cytoskeleton And Increases Pancreatic Cancer Growth And Metastasis., Poomy Pandey, Satyanarayana Rachagani, Srustidhar Das, Parthasarathy Seshacharyulu, Yuri Sheinin, Naava Naslavsky, Zenggang Pan, Brittney L. Smith, Haley L. Peters, Prakash Radhakrishnan, Nicole R. Mckenna, Sai Srinivas Panapakkam Giridharan, Dhanya Haridas, Sukhwinder Kaur, Michael A. Hollingsworth, Richard G. Macdonald, Jane L. Meza, Steve Caplan, Surinder K. Batra, Joyce C. Solheim

Journal Articles: Biochemistry & Molecular Biology

Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine. Examination of matched human primary tumor-liver metastasis pairs showed that 38.1% of the patients had positive APLP2 expression in both the primary tumor and the corresponding liver metastasis. Stable knock-down of APLP2 expression (with inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to migrate and invade. Loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells. Down-regulation of APLP2 …

Predictors And Outcomes Of Mycobacterium Tuberculosis Bacteremia Among Patients With Hiv And Tuberculosis Co-Infection Enrolled In The Actg A5221 Stride Study., John A. Crump, Xingye Wu, Michelle A. Kendall, Prudence D. Ive, Johnstone J. Kumwenda, Beatriz Grinsztejn, Ute Jentsch, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts)/mm(3). We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia.

METHODS: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status.

RESULTS: …

Age-Related Factors Influencing The Occurrence Of Undernutrition In Northeastern Ethiopia, Abraham Degarege, Elifaged Hailemeskel, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Undernutrition is a major public health problem on the globe particularly in the developing regions. The objective of the current study was to assess the prevalence of undernutrition in different age groups and examine the relationship of the disease to parasitic and socioeconomic factors among communities in Harbu Town, northeastern Ethiopia.

METHODS: Stool samples of the study participants were examined for intestinal helminth infections using the Kato-Katz method. Blood specimens were diagnosed for Plasmodium infection using CareStartTM Malaria Pf/Pv Combo test. The blood type was determined from blood samples using antisera A and antisera B. In addition, the height …

Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel

Journal Articles: Oncology and Hematology

No abstract provided.

Clinical Presentation Of Patients With Ebola Virus Disease In Conakry, Guinea, Elhadj Ibrahima Bah, Marie-Claire Lamah, Tom Fletcher, Shevin T. Jacob, David Brett-Major, Amadou Alpha Sall, Nahoko Shindo, William A. Fischer, Francois Lamontagne, Sow Mamadou Saliou, Daniel G. Bausch, Barry Moumié, Tim Jagatic, Armand Sprecher, James V. Lawler, Thierry Mayet, Frederique A. Jacquerioz, María F. Méndez Baggi, Constanza Vallenas, Christophe Clement, Simon Mardel, Ousmane Faye, Oumar Faye, Baré Soropogui, Nfaly Magassouba, Lamine Koivogui, Ruxandra Pinto, Robert A. Fowler

Journal Articles: Epidemiology

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date.

METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors.

RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed …

Undernutrition And Associated Risk Factors Among School Age Children In Addis Ababa, Ethiopia, Dawit Degarege, Abraham Degarege, Abebe Animut

Journal Articles: Epidemiology

BACKGROUND: Causes of child undernutrition are diverse and change in space and time. Investigating current determinants of undernutrition remains vital to design an effective intervention strategy. The study assessed prevalence of undernutrition and its associated factors among children living in Addis Ababa, Ethiopia.

METHODS: A community based cross-sectional study was conducted in 459 school age children and their parents or caregivers living in Lideta sub-city, Addis Ababa, Ethiopia. Participants were selected using a multi-stage simple random sampling technique. Height and weight of children was measured and their parents or care givers were interviewed for factors associated with undernutrition.

RESULTS: About …

Comparison Of Individual And Pooled Urine Samples For Estimating The Presence And Intensity Of Schistosoma Haematobium Infections At The Population Level, Abraham Degarege, Berhanu Erko, Zeleke Mekonnen, Mengistu Legesse, Yohannes Negash, Jozef Vercruysse, Bruno Levecke

Journal Articles: Epidemiology

BACKGROUND: There is a lack of cost-effective diagnostic strategies to evaluate whether mass drug administration (MDA) programmes to control Schistosoma haematobium progress as anticipated. The purpose of this study is to provide a proof-of-principle for examination of pooled urine samples as a strategy for rapid assessment of presence and intensity of Schistosoma haematobium infections at the population level.

METHODS: A total of 640 urine samples were collected from 520 school-aged children (520 at baseline and 120 at follow-up) during a clinical trial that was designed to assess the efficacy of praziquantel against Schistosoma haematobium infections in Ethiopia. Individual and pooled …