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Dean A VanNasdale, Ann E Elsner, Victor E Malinovsky, Todd D Peabody, Kimberly D Kohne, Bryan P Haggerty, Christopher A Clark
SIGNIFICANCE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Complementary imaging techniques can be used to better characterize and quantify pathological changes associated with AMD. By assessing specific light-tissue interactions, polarization-sensitive imaging can be used to detect tissue disruption early in the disease process. PURPOSE: The aim of this study was to compare variability in central macular polarization properties in patients with nonexudative AMD and age-matched control subjects...
March 21, 2018: Optometry and Vision Science: Official Publication of the American Academy of Optometry
Balaji Krishnan, Rakez Kayed, Giulio Taglialatela
Introduction: Phospholipase D (PLD), a lipolytic enzyme that breaks down membrane phospholipids, is also involved in signaling mechanisms downstream of seven transmembrane receptors. Abnormally elevated levels of PLD activity are well-established in Alzheimer's disease (AD), implicating the two isoforms of mammalian phosphatidylcholine cleaving PLD (PC-PLD1 and PC-PLD2). Therefore, we took a systematic approach of investigating isoform-specific expression in human synaptosomes and further investigated the possibility of therapeutic intervention using preclinical studies...
2018: Alzheimer's & Dementia: Translational Research & Clinical Interventions
Brian B Silver, Celeste M Nelson
Cancer is a complex, heterogeneous group of diseases that can develop through many routes. Broad treatments such as chemotherapy destroy healthy cells in addition to cancerous ones, but more refined strategies that target specific pathways are usually only effective for a limited number of cancer types. This is largely due to the multitude of physiological variables that differ between cells and their surroundings. It is therefore important to understand how nature coordinates these variables into concerted regulation of growth at the tissue scale...
2018: Frontiers in Cell and Developmental Biology
Alireza Khodadadi-Jamayran, Betul Akgol-Oksuz, Yelena Afanasyeva, Adriana Heguy, Marae Thompson, Karina Ray, Ariadna Giro-Perafita, Irma Sánchez, Xifeng Wu, Debu Tripathy, Anne Zeleniuch-Jacquotte, Aristotelis Tsirigos, Francisco J Esteva
MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage...
February 27, 2018: Oncotarget
Andrew W Artenstein, Jennifer Friderici, Paul Visintainer
Introduction: Spinal epidural abscess (SEA), a highly morbid and potentially lethal deep tissue infection of the central nervous system has more than tripled in incidence over the past decade. Early recognition at the point of initial clinical presentation may prevent irreversible neurologic injury or other serious, adverse outcomes. To facilitate early recognition of SEA, we developed a predictive scoring model. Methods: Using data from a 10-year, retrospective, case-control study of adults presenting for care at a tertiary-care, regional, academic medical center, we used the Integrated Discrimination Improvement Index (IDI) to identify candidate discriminators and created a multivariable logistic regression model, refined based on p-value significance...
March 2018: Western Journal of Emergency Medicine
Piotr Donizy, Konrad Pagacz, Jakub Marczuk, Wojciech Fendler, Adam Maciejczyk, Agnieszka Halon, Rafal Matkowski
Background: FOXP1 is a pleiotropic protein that plays important roles in immune responses (B-cell development regulation and differentiation of monocyte), organ development (cardiac valves, lung, and esophagus), and neuronal development. Besides being the primary regulator of normal human tissue development, FOXP1 also plays a role in tumorigenesis. However, the potential value of FOXP1 expression in tumor prognosis remains controversial. FOXP1 expression was assessed in tumor cells (TCs) and stromal cells (SCs) of cutaneous melanomas with the aim of analyzing the associations between FOXP1 expression and clinicopathological characteristics...
2018: OncoTargets and Therapy
Jarunya Samsuwan, Tachapol Muangsub, Pattamawadee Yanatatsaneejit, Apiwat Mutirangura, Nakarin Kitkumthorn
According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord...
March 9, 2018: Forensic Science International
Cristina Guillín-Amarelle, Antía Fernández-Pombo, Sofía Sánchez-Iglesias, David Araújo-Vilar
The nuclear lamina is a complex reticular structure that covers the inner face of the nucleus membrane in metazoan cells. It is mainly formed by intermediate filaments called lamins, and exerts essential functions to maintain the cellular viability. Lamin A/C provides mechanical steadiness to the nucleus and regulates genetic machinery. Laminopathies are tissue-specific or systemic disorders caused by variants in LMNA gene (primary laminopathies) or in other genes encoding proteins which are playing some role in prelamin A maturation or in lamin A/C function (secondary laminopathies)...
March 20, 2018: Nucleus
Jionghuang Chen, Ting Zhao, Shengnan Jia, Senhao Zhou, Liangjing Zhou, Shaowen Wang, Guoping Ding, Guixing Jiang, Liping Cao
Background: P38α is a ubiquitous protein kinase, which plays diverse roles in cancers. Surprisingly, P38α functions vary markedly in different cancers (e.g., cancer suppressor vs cancer promoter). However, there is no report on the expression of P38α, the family's most important member, in pancreatic ductal adenocarcinoma (PDAC) and its association with clinicoathological parameters and patients' prognosis. Materials and methods: We retrospectively analyzed 152 patients who underwent surgery and were pathologically diagnosed with PDAC from September 2013 to September 2015...
2018: Journal of Cancer
Divyen K Shah, Vennila Ponnusamy, Jane Evanson, Olga Kapellou, Georgia Ekitzidou, Neelam Gupta, Paul Clarke, Adina T Michael-Titus, Ping K Yip
Aims and hypothesis: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of death and disability in newborns. Mild therapeutic hypothermia (TH) is safe and effective; however, there are no tissue biomarkers available at the bedside to select babies for treatment. The aim of this study was to show that it is feasible to study plasma neurofilament light (NfL) levels from newborns and to evaluate their temporal course. Hypothesis: Raised plasma NFL protein levels from newborns who undergo TH after HIE are associated with abnormal MRI outcomes...
2018: Frontiers in Neurology
Olga Y Rybina, Yakov M Rozovsky, Ekaterina R Veselkina, Elena G Pasyukova
Molecular mechanisms governing gene expression and defining complex phenotypes are central to understanding the basics of development and aging. Here, we demonstrate that naturally occurring polymorphisms of the Lim3 regulatory region that are associated with variation in gene expression and Drosophila lifespan control are located exclusively in the Polycomb response element (PRE). We find that the Polycomb group (PcG) protein Polycomb (PC) is bound to the PRE only in embryos where Lim3 is present in both repressed and active states...
March 16, 2018: Biochimica et Biophysica Acta
Maria Giulia Bacalini, Claudio Franceschi, Davide Gentilini, Francesco Ravaioli, Xiaoyuan Zhou, Daniel Remondini, Chiara Pirazzini, Cristina Giuliani, Elena Marasco, Noémie Gensous, Anna Maria Di Blasio, Ewa Ellis, Roberto Gramignoli, Gastone Castellani, Miriam Capri, Stephen Strom, Christine Nardini, Matteo Cescon, Gian Luca Grazi, Paolo Garagnani
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes...
March 15, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Monica G Ferrini, Eduardo Garcia, Andrea Abraham, Jorge N Artaza, Sabine Nguyen, Jacob Rajfer
INTRODUCTION: COMP-4 is a natural compound-based dietary supplement consisting of the combination of ginger, Paullinia cupana, muira puama and l-citrulline, which when given long-term has been shown in the aged rat to a) upregulate iNOS in the penile smooth muscle cells (SMC), b) reverse the corporal SMC apoptosis and fibrosis associated with corporal veno-occlusive dysfunction (CVOD), and c) improve resulting erectile function. To elucidate the mechanism of how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a rat corporal primary SMC culture to determine its effect on NOS, soluble guanylate cyclase (sGC), cGMP and the phosphodiesterase 5 enzyme (PDE5)...
March 15, 2018: Nitric Oxide: Biology and Chemistry
Chenju Yi, Jérémy Theillon, Annette Koulakoff, Hugues Berry, Christian Giaume
Intercellular communication through gap junction channels plays a key role in cellular homeostasis and in synchronizing physiological functions, a feature that is modified in number of pathological situations. In the brain, astrocytes are the cell population that expresses the highest amount of gap junction proteins, named connexins. Several techniques have been used to assess the level of gap junctional communication in astrocytes, but so far they remain very difficult to apply in adult brain tissue. Here, using specific loading of astrocytes with sulforhodamine 101, we adapted the gap-FRAP (Fluorescence Recovery After Photobleaching) to acute hippocampal slices from 9 month-old adult mice...
March 15, 2018: Journal of Neuroscience Methods
John D Koerner, Dessislava Z Markova, Greg D Schroeder, Brian P Calio, Anuj Shah, Corbin W Brooks, Alexander R Vaccaro, D Greg Anderson, Chris K Kepler
BACKGROUND CONTEXT: The systemic response regarding cytokine expression after application of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in a rat spinal fusion model has recently been defined1 , but the local response has not. Defining the local cytokine and growth factor response at the fusion site will help explain the roles of these molecules in the fusion process, as well as that of rhBMP-2. Our hypothesis is that application of rhBMP-2 to the fusion site will alter the local levels of cytokines and growth factors throughout the fusion process, in a manner that is different than the systemic response given the tissue-specific effects of rhBMP-2...
March 14, 2018: Spine Journal: Official Journal of the North American Spine Society
Olivier Villemain, Mafalda Correia, Elie Mousseaux, Jérome Baranger, Samuel Zarka, Ilya Podetti, Gilles Soulat, Thibaud Damy, Albert Hagège, Mickael Tanter, Mathieu Pernot, Emmanuel Messas
OBJECTIVES: The goal of our study was to investigate the potential of myocardial shear wave imaging (SWI) to quantify the diastolic myocardial stiffness (MS) (kPa) noninvasively in adult healthy volunteers (HVs) and its physiological variation with age, and in hypertrophic cardiomyopathy (HCM) populations with heart failure and preserved ejection function (HFpEF). BACKGROUND: MS is an important prognostic and diagnostic parameter of the diastolic function. MS is affected by physiological changes but also by pathological alterations of extracellular and cellular tissues...
March 9, 2018: JACC. Cardiovascular Imaging
N Touati, P Schöffski, S Litière, I Judson, S Sleijfer, W T van der Graaf, A Italiano, N Isambert, T Gil, J Y Blay, D Stark, T Brodowicz, S Marréaud, A Gronchi
AIMS: Epithelioid sarcoma is a soft tissue sarcoma associated with a high rate of local recurrence after wide resection and high incidence of distant metastasis. Little is known about the clinical course and response to systemic treatments in epithelioid sarcoma patients. We carried out a retrospective analysis of clinical data from epithelioid sarcoma patients to provide a reference for the design of future epithelioid sarcoma-specific studies. PATIENTS AND METHODS: Data from patients with epithelioid sarcoma entered in prospective multi-sarcoma phase II/III trials were pooled: EORTC trial 62012 (doxorubicin versus doxorubicin/ifosfamide), 62043 (pazopanib), 62072 (pazopanib versus placebo) and 62091 (doxorubicin versus trabectedin)...
March 15, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
Meagan E Tibbo, Cody C Wyles, Peter S Rose, Franklin H Sim, Matthew T Houdek, Michael J Taunton
BACKGROUND: Synovial chondromatosis (SC) is a rare disease involving cartilaginous metaplasia of synovial tissue. Treatment via synovectomy and loose body removal alone results in elevated recurrence rates, with up to 1 in 5 patients requiring conversion to a hip arthroplasty. The purpose of this study is to investigate outcomes of hip arthroplasty in the setting of SC, focusing on (1) disease-specific survival, (2) implant survivorship and complications, and (3) clinical outcomes. METHODS: We identified 26 patients with histologically confirmed SC who underwent hip arthroplasty between 1970 and 2015...
February 15, 2018: Journal of Arthroplasty
E Sayit, A T Sayit, M Bagir, Y Terzi
BACGROUND: Ulnar variance, or the difference in height between the joint surfaces of the distal radius and ulna, may play a role in several diseases of the wrist. HYPOTHESIS: This study was to conduct a detailed analysis of ulnar variance in a wider case series by dividing the patients' radiographs into groups according to age, gender, and side. MATERIALS AND METHODS: Twenty groups were created in order to investigate the change of ulnar variance according to age, gender, and side...
March 13, 2018: Orthopaedics & Traumatology, Surgery & Research: OTSR
Valérie Haydont, Bruno A Bernard, Nicolas O Fortunel
Ageing is today a major societal concern that is intrinsically associated with the increase of life expectancy. Outside the context of severe degenerative diseases that affect the elderly populations, normal visible signs of ageing, notably skin sagging and wrinkles, influence the social and individual perception of peoples. Accordingly, there is a strong demand for researches on skin ageing. Deciphering the cellular and molecular processes of skin evolution through ageing is thus an active scientific domain, at the frontier of tissue developmental and ageing biology...
March 13, 2018: Mechanisms of Ageing and Development
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