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Disease modelling

Charles D Warne, Sophie G Zaloumis, Nadine A Bertalli, Martin B Delatycki, Amanda J Nicoll, Christine E McLaren, John L Hopper, Graham G Giles, Greg J Anderson, John K Olynyk, Lawrie W Powell, Katrina J Allen, Lyle C Gurrin
BACKGROUND AND AIM: Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably due to the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p...
October 26, 2016: Journal of Gastroenterology and Hepatology
Spyridon Chavlis, Panagiotis C Petrantonakis, Panayiota Poirazi
The hippocampus plays a key role in pattern separation, the process of transforming similar incoming information to highly dissimilar, non-overlapping representations. Sparse firing granule cells (GCs) in the dentate gyrus (DG) have been proposed to undertake this computation, but little is known about which of their properties influence pattern separation. Dendritic atrophy has been reported in diseases associated with pattern separation deficits, suggesting a possible role for dendrites in this phenomenon...
October 26, 2016: Hippocampus
Ji Yi, Zhen Puyang, Liang Feng, Lian Duan, Peiji Liang, Vadim Backman, Xiaorong Liu, Hao F Zhang
Purpose: Elastic light backscattering spectroscopy (ELBS) has exquisite sensitivity to the ultrastructural properties of tissue and thus has been applied to detect various diseases associated with ultrastructural alterations in their early stages. This study aims to test whether ELBS can detect early damage in retinal ganglion cells (RGCs). Methods: We used a mouse model of partial optic nerve crush (pONC) to induce rapid RGC death. We confirmed RGC loss by axon counting and characterized the changes in retinal morphology by optical coherence tomography (OCT) and in retinal function by full-field electroretinogram (ERG), respectively...
October 1, 2016: Investigative Ophthalmology & Visual Science
Paolo Fusar-Poli, Grazia Rutigliano, Daniel Stahl, André Schmidt, Valentina Ramella-Cravaro, Shetty Hitesh, Philip McGuire
Importance: Pretest risk estimation is routinely used in clinical medicine to inform further diagnostic testing in individuals with suspected diseases. To our knowledge, the overall characteristics and specific determinants of pretest risk of psychosis onset in individuals undergoing clinical high risk (CHR) assessment are unknown. Objectives: To investigate the characteristics and determinants of pretest risk of psychosis onset in individuals undergoing CHR assessment and to develop and externally validate a pretest risk stratification model...
October 26, 2016: JAMA Psychiatry
Peter Sandner, Peter Berger, Christoph Zenzmaier
Fibrotic diseases cause high rates of morbidity and mortality, and their incidence increases with age. Despite intense research and development efforts, effective and well-tolerated antifibrotic treatments are scarce. Transforming growth factor-β signaling, which is widely considered the most important profibrotic factor, causes a pro-oxidant shift in redox homeostasis and a concomitant decrease in nitric oxide (NO) signaling. The NO/cyclic guanosine monophosphate (cGMP) signaling cascade plays a pivotal role in the regulation of cell and organ function in whole-body hemostasis...
October 27, 2016: Gerontology
Siham Bibi, Yanyan Zhang, Caroline Hugonin, Mallorie Depond Mangean, Liang He, Ghaith Wedeh, Jean-Marie Launay, Sjoerd Van Rijn, Thomas Würdinger, Fawzia Louache, Michel Arock
Systemic mastocytosis are rare neoplasms characterized by accumulation of mast cells in at least one internal organ. The majority of systemic mastocytosis patients carry KIT D816V mutation, which activates constitutively the KIT receptor. Patient with advanced forms of systemic mastocytosis, such as aggressive systemic mastocytosis or mast cell leukemia, are poorly treated to date. Unfortunately, the lack of in vivo models reflecting KIT D816V+ advanced disease hampers pathophysiological studies and preclinical development of new therapies for such patients...
October 22, 2016: Oncotarget
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
Salma Ayoub, Giovanni Ferrari, Robert C Gorman, Joseph H Gorman, Frederick J Schoen, Michael S Sacks
Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling...
September 15, 2016: Comprehensive Physiology
Cintia Koerich, Alacoque Lorenzini Erdmann
Objective: to understand significances attributed by nurses who manage nursing care to the individual affected by cardiovascular disease to relations, interactions and associations of the educational practices in a cardiovascular reference hospital. To elaborate a theoretical explanatory model based on significances attributed in the light of the complex thinking. Method: qualitative study, which used Theory Based on Data (TBD) as methodological reference. Twenty-two professionals of nursing participated in the study...
September 2016: Revista Brasileira de Enfermagem
Denise F R Rawcliffe, Lennart Österman, Hans Lindsten, Monica Holmberg
Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intronic one-base mutation in the iron-sulfur cluster assembly (ISCU) gene, resulting in aberrant splicing. The incorrectly spliced transcripts contain a 100 or 86 bp intron sequence encoding a non-functional ISCU protein, which leads to defects in several Fe-S containing proteins in the respiratory chain and the TCA cycle. The symptoms in HML are restricted to skeletal muscle, and it has been proposed that this effect is due to higher levels of incorrectly spliced ISCU in skeletal muscle compared with other energy-demanding tissues...
2016: PloS One
Tomas Maria Perez-Porcuna, Hélio Doyle Pereira-da-Silva, Carlos Ascaso, Adriana Malheiro, Samira Bührer, Flor Martinez-Espinosa, Rosa Abellana
INTRODUCTION: For adequate disease control the World Health Organization has proposed the diagnosis and treatment of latent tuberculous infection (LTBI) in groups of risk of developing the disease such as children. There is no gold standard (GS) test for the diagnosis of LTBI. The objective of this study was to estimate the prevalence of LTBI in young children in contact with a household case of tuberculosis (TB-HCC) and determine the accuracy and precision of the Tuberculin Skin Test (TST) and QuantiFERON-TB Gold in-tube (QFT) used in the absence of a GS...
2016: PloS One
Viviane Coutinho Meneguzzi, Claudiney Biral Dos Santos, Gustavo Rocha Leite, Blima Fux, Aloísio Falqueto
Cutaneous leishmaniasis (CL) is caused by a protozoan of the genus Leishmania and is transmitted by sand flies. The state of Espírito Santo (ES), an endemic area in southeast Brazil, has shown a considerably high prevalence in recent decades. Environmental niche modelling (ENM) is a useful tool for predicting potential disease risk. In this study, ENM was applied to sand fly species and CL cases in ES to identify the principal vector and risk areas of the disease. Sand flies were collected in 466 rural localities between 1997 and 2013 using active and passive capture...
2016: PloS One
Thanh Nguyen, Asim Bhatti, Samuel Yang, Saeid Nahavandi
This paper introduces an approach to classification of RNA-seq read counts using grey relational analysis (GRA) and Bayesian Gaussian process (GP) models. Read counts are transformed to microarray-like data to facilitate normal-based statistical methods. GRA is designed to select differentially expressed genes by integrating outcomes of five individual feature selection methods including two-sample t-test, entropy test, Bhattacharyya distance, Wilcoxon test and receiver operating characteristic curve. GRA performs as an aggregate filter method through combining advantages of the individual methods to produce significant feature subsets that are then fed into a nonparametric GP model for classification...
2016: PloS One
Janet Bouttell, James Lewsey, Claudia Geue, Grace Antony, Andrew Briggs, Gerry McCartney, Sharon Hutchinson, Lesley Graham, Mathis Heydtmann
Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission...
2016: PloS One
Sarah E Goglin, Ramin Farzaneh-Far, Elissa S Epel, Jue Lin, Elizabeth H Blackburn, Mary A Whooley
BACKGROUND: Short telomere length independently predicts mortality in patients with coronary heart disease. Whether 5-year change in telomere length predicts subsequent mortality in patients with coronary heart disease has not been evaluated. METHODS: In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline and after five years of follow-up. We divided the sample into tertiles of telomere change: shortened, maintained or lengthened...
2016: PloS One
Wendy S Bibeau, Haoda Fu, April D Taylor, Anita Y M Kwan
BACKGROUND: Medication adherence is pivotal for the successful treatment of diabetes. However, medication adherence remains a major concern, as nonadherence is associated with poor health outcomes. Studies have indicated that increasing patients' share of medication costs significantly reduces adherence. Little is known about a potential out-of-pocket (OOP) cost threshold where substantial reduction in adherence may occur. OBJECTIVE: To examine the impact of diabetes OOP pharmacy costs on antihyperglycemic medication adherence and identify the potential threshold at which significant reduction in adherence may occur among patients with type 2 diabetes mellitus (T2DM)...
November 2016: Journal of Managed Care & Specialty Pharmacy
JaeJin An
BACKGROUND: Current evidence suggests that patient-centered medical homes (PCMHs) potentially increase overall quality of disease management, including preventive care. However, there are mixed findings regarding quality of diabetes care, and little evidence exists with respect to the effect of PCMHs on medication adherence in patients with diabetes. OBJECTIVE: To investigate associations between PCMHs and process measures of diabetes care, as well as adherence to oral hypoglycemic agents (OHAs) in patients with diabetes in a nationally representative U...
November 2016: Journal of Managed Care & Specialty Pharmacy
Alexander Kirschenbaum, Sudeh Izadmehr, Shen Yao, Kieley L O'Connor-Chapman, Alan Huang, Elias M Gregoriades, Shoshana Yakar, Alice C Levine
Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the RANK/RANKL/OPG system...
October 26, 2016: Endocrinology
Luis Sendra Gisbert, Antonio Miguel Matas, Luis Sabater Ortí, María José Herrero Cervera, Laura Sabater Olivas, Eva María Montalvá Orón, Matteo Frasson, Rafael Abargues López, Rafael López-Andújar, Eduardo García-Granero Ximénez, Salvador Francisco Aliño Pellicer
: Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. Immunosuppressant drugs permitted improving organ transplantation but they cannot completely solve the problem and their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required...
October 26, 2016: Liver Transplantation
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