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https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#1
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155921/aridification-as-a-driver-of-biodiversity-a-case-study-for-the-cycad-genus-dioon-zamiaceae
#2
José Said Gutiérrez-Ortega, Takashi Yamamoto, Andrew P Vovides, Miguel Angel Pérez-Farrera, José F Martínez, Francisco Molina-Freaner, Yasuyuki Watano, Tadashi Kajita
Background and Aims: Aridification is considered a selective pressure that might have influenced plant diversification. It is suggested that plants adapted to aridity diversified during the Miocene, an epoch of global aridification (≈15 million years ago). However, evidence supporting diversification being a direct response to aridity is scarce, and multidisciplinary evidence, besides just phylogenetic estimations, is necessary to support the idea that aridification has driven diversification...
November 16, 2017: Annals of Botany
https://www.readbyqxmd.com/read/29155581/phosphorescence-control-mediated-by-molecular-rotation-and-aurophilic-interactions-in-amphidynamic-crystals-of-1-4-bis-tri-p-fluorophenyl-phosphane-gold-i-ethynyl-benzene
#3
Mingoo Jin, Tim S Chung, Tomohiro Seki, Hajime Ito, Miguel A Garcia-Garibay
Here we present a structural design aimed at the control of phosphorescence emission as the result of changes in molecular rotation in a crystalline material. The proposed strategy includes the use of aurophilic interactions, both as a crystal engineering tool and as sensitive emission probe, and the use of a dumbbell-shaped architecture intended to create a low packing density region that permits the rotation of a central phenylene. Molecular rotor 1 with of a central 1,4-diethynylphenylene rotator linked to two gold(I) triphenylphosphane complexes was prepared and its structure confirmed by single crystal X-ray diffraction (XRD), which revealed chains mediated by dimeric aurophilic interactions...
November 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29155385/local-low-dose-urokinase-thrombolysis-for-the-management-of-hemodynamically-stable-pulmonary-embolism-with-right-ventricular-dysfunction
#4
Sara Alcántara Carmona, Marina Pérez Redondo, Luis Nombela Franco, Rocío González Costero, Bárbara Balandín Moreno, Miguel Valdivia de la Fuente, Santiago Méndez Alonso, Agustín García Suárez, Ana Royuela
AIMS: To evaluate the effectiveness of local low-dose urokinase thrombolysis (LLDUT) in hemodynamically stable pulmonary embolism with right ventricular dysfunction (RVD). METHODS AND RESULTS: Prospective study. LLDUT with a 200,000 IU bolus followed by a 100,000 IU/h infusion. Treatment duration was determined through radiological control performed 48-72h into treatment. Follow-up echocardiogram was performed within seven days after LLDUT completion. Evolution of thrombus burden, pulmonary artery pressures (PAP) and RVD were studied, and hemorrhagic complications and mortality were recorded...
November 21, 2017: EuroIntervention
https://www.readbyqxmd.com/read/29155337/photodynamic-therapy-in-fibrosarcoma-balb-c-animal-model-observation-of-the-rebound-effect
#5
Etcheverry María Eugenia, Pasquale Miguel Ángel, Gutiérrez Anabella, Bibé Solange, Ponzinibbio Carlos, Poteca Horacio, Garavaglia Mario
In vivo spectrofluorometric analysis during photodynamic therapy (PDT) is a fundamental tool to obtain information about the drug bleaching kinetics. Using a portable spectrofluorometer with an excitation source emitting at 400nm wavelength and a spectral analyzer ranging from 500nm to 800nm, the evolution of the meta-tetra(hydroxyphenyl) chlorin (m-THPC) photosensitizer fluorescence spectrum at the tumoral tissue of BALB/c murines with fibrosarcoma located at their flank was followed up. Ex vivo fluorescence measurements of the tumor and skin were also performed with the aim of better characterizing the in vivo signal at different parts of the tumor...
November 16, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29155265/neuroanatomical-distribution-and-function-of-the-vasopressin-v1b-receptor-in-the-rat-brain-deciphered-using-specific-fluorescent-ligands
#6
Maithé Corbani, Rafik Marir, Miguel Trueba, Magda Chafai, Anne Vincent, Amélie M Borie, Michel G Desarménien, Yoichi Ueta, Csaba Tomboly, Aleksandra Olma, Maurice Manning, Gilles Guillon
It is now accepted that vasopressin, through V1A/V1B receptors, centrally regulates cognitive functions such as memory, affiliation, stress, fear and depression. However, the respective roles of these receptor isoforms and their contribution to stress-related pathologies remain uncertain. The development of new therapeutic treatments requires a precise knowledge of the distribution of these receptors within the brain, which has been so far hampered by the lack of selective V1B markers. In the present study, we have determined the pharmacological properties of three new potent rat V1B fluorescent ligands and demonstrated that they constitute valuable tools for simultaneous visualization and activation of native V1B receptors in living rat brain tissue...
November 16, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29155226/interaction-between-cardiovascular-risk-factors-and-body-mass-index-and-10-year-incidence-of-cardiovascular-disease-cancer-death-and-overall-mortality
#7
Maria Barroso, Albert Goday, Rafel Ramos, Alejandro Marín-Ibañez, Maria Jesús Guembe, Fernando Rigo, Maria José Tormo-Díaz, Conchi Moreno-Iribas, Joan Josep Cabré, Antonio Segura, Jose Miguel Baena-Díez, Agustín Gómez de la Cámara, José Lapetra, Miquel Quesada, María José Medrano, Jesús Berjón, Guillem Frontera, Diana Gavrila, Aurelio Barricarte, Josep Basora, José María García, Manel García-Lareo, David Lora-Pablos, Eduardo Mayoral, María Grau, Jaume Marrugat
The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination...
November 16, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/29155207/cytotoxic-effect-of-the-serotonergic-drug-1-1-naphthyl-piperazine-against-melanoma-cells
#8
Ana Catarina Menezes, Manuela Carvalheiro, José Miguel P Ferreira de Oliveira, Andreia Ascenso, Helena Oliveira
1-(1-Naphthyl)piperazine (1-NPZ) is a serotonergic derivative of quipazine acting both as antagonist and agonist of different serotonin receptors, with promising results for the management of skin cancer. In this work, we studied the effect of 1-NPZ on human MNT-1 melanoma cells by evaluating its effects on cell viability, ability to form colonies, cell cycle dynamics, reactive oxygen species (ROS) production and apoptosis. Treatment of MNT-1 cells with 1-NPZ for 24h decreased cell viability and induced apoptosis in a dose-dependent manner...
November 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29155078/radial-asymmetries-in-population-receptive-field-size-and-cortical-magnification-factor-in-early-visual-cortex
#9
Maria Fatima Silva, Jan W Brascamp, Sónia Ferreira, Miguel Castelo-Branco, Serge O Dumoulin, Ben M Harvey
Human visual cortex does not represent the whole visual field with the same detail. Changes in receptive field size, population receptive field (pRF) size and cortical magnification factor (CMF) with eccentricity are well established, and associated with changes in visual acuity with eccentricity. Visual acuity also changes across polar angle. However, it remains unclear how RF size, pRF size and CMF change across polar angle. Here, we examine differences in pRF size and CMF across polar angle in V1, V2 and V3 using pRF modeling of human fMRI data...
November 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/29154940/ebulin-rp-a-novel-member-of-the-ebulin-gene-family-with-low-cytotoxicity-as-a-result-of-deficient-sugar-binding-domains
#10
Rosario Iglesias, J Miguel Ferreras, Antimo Di Maro, Lucía Citores
BACKGROUND: Sambucus ebulus is a rich source of ribosome-inactivating proteins (RIPs) and RIP-related lectins generated from multiple genes. These proteins differ in their structure, enzymatic activity and sugar binding specificity. METHODS: We have purified and characterized ebulin-RP from S. ebulus leaves and determined the amino acid sequence by cDNA cloning. Cytotoxicity was studied in a variety of cancer cells and a comparative study of the ability of ebulin-RP to bind sugars using "in vitro" and "in silico" approaches was performed...
November 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154812/under-stressful-conditions-activation-of-the-ionotropic-p2x7-receptor-differentially-regulates-gaba-and-glutamate-release-from-nerve-terminals-of-the-rat-cerebral-cortex
#11
Aurora R Barros-Barbosa, Ângela Oliveira, M Graça Lobo, J Miguel Cordeiro, Paulo Correia-de-Sá
γ-Aminobutyric acid (GABA) and glutamate (Glu) are the main inhibitory and excitatory neurotransmitters in the central nervous system (CNS), respectively. Fine tuning regulation of extracellular levels of these amino acids is essential for normal brain activity. Recently, we showed that neocortical nerve terminals from patients with epilepsy express higher amounts of the non-desensitizing ionotropic P2X7 receptor. Once activated by ATP released from neuronal cells, the P2X7 receptor unbalances GABAergic vs...
November 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29153975/optimisation-of-empirical-antimicrobial-therapy-in-patients-with-haematological-malignancies-and-febrile-neutropenia-how-long-study-an-open-label-randomised-controlled-phase-4-trial
#12
Manuela Aguilar-Guisado, Ildefonso Espigado, Almudena Martín-Peña, Carlota Gudiol, Cristina Royo-Cebrecos, José Falantes, Lourdes Vázquez-López, María Isabel Montero, Clara Rosso-Fernández, María de la Luz Martino, Rocío Parody, José González-Campos, Sebastián Garzón-López, Cristina Calderón-Cabrera, Pere Barba, Nancy Rodríguez, Montserrat Rovira, Enrique Montero-Mateos, Jordi Carratalá, José Antonio Pérez-Simón, José Miguel Cisneros
BACKGROUND: Continuation of empirical antimicrobial therapy (EAT) for febrile neutropenia in patients with haematological malignancies until neutrophil recovery could prolong the therapy unnecessarily. We aimed to establish whether EAT discontinuation driven by a clinical approach regardless of neutrophil recovery would optimise the duration of therapy. METHODS: We did an investigator-driven, superiority, open-label, randomised, controlled phase 4 clinical trial in six academic hospitals in Spain...
November 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29153962/sonographic-criteria-predictive-of-malignant-thyroid-nodules-which-lesions-should-be-biopsied
#13
Carlos Miguel Oliveira, Rui Alves Costa, Miguel Patrício, Amélia Estêvão, Bruno Graça, Filipe Caseiro-Alves
RATIONALE AND OBJECTIVES: The objective of this study was to evaluate the ultrasound features of thyroid nodules and their association with malignancy, focusing on establishing feature-oriented ultrasound criteria to determine proper management of a thyroid nodule. MATERIALS AND METHODS: A sample of 379 thyroid nodules were biopsied (from a total of 357 patients aged 59.8 ± 14.8 years) and 300 were included in the final study (271 benign nodules and 29 malignant ones)...
November 16, 2017: Academic Radiology
https://www.readbyqxmd.com/read/29153843/aberrant-activation-of-a-gastrointestinal-transcriptional-circuit-in-prostate-cancer-mediates-castration-resistance
#14
Shipra Shukla, Joanna Cyrta, Devan A Murphy, Edward G Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W P Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P Koche, Anuradha Gopalan, Deyou Zheng, Mark A Rubin, Howard I Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A...
November 3, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29153753/an-easy-assessment-of-frailty-at-baseline-independently-predicts-prognosis-in-very-elderly-patients-with-acute-coronary-syndromes
#15
Oriol Alegre, Francesc Formiga, Ramón López-Palop, Francisco Marín, María T Vidán, Manuel Martínez-Sellés, Antoni Carol, Alessandro Sionis, Pablo Díez-Villanueva, Jaime Aboal, Anna Palau-Vendrel, Héctor Bueno, Angel Perez Rivera, Juan Sanchís, Emad Abu-Assi, Miguel Corbí, Juan C Castillo, Jordi Bañeras, Violeta González-Salvado, Àngel Cequier, Albert Ariza-Solé
BACKGROUND: Information about the impact of frailty in patients with acute coronary syndromes (ACS) is scarce. No study has assessed the prognostic impact of frailty as measured by the FRAIL scale in very elderly patients with ACS. METHODS: The prospective multicenter LONGEVO-SCA registry included unselected patients with ACS aged 80 years or older. A comprehensive geriatric assessment was performed during hospitalization, including frailty assessment by the FRAIL scale...
November 16, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29153618/advantages-of-a-prospective-multidisciplinary-approach-in-transcatheter-aortic-valve-implantation-eight-years-of-experience
#16
Cátia Costa, Rui Campante Teles, João Brito, José Pedro Neves, Henrique Mesquita Gabriel, Miguel Abecassis, Regina Ribeiras, João Abecasis, Tiago Nolasco, Maria da Conceição Furstenau, Nélson Vale, António Tralhão, Sérgio Madeira, João Mesquita, Carla Saraiva, Rita Calé, Manuel Almeida, Ana Aleixo, Miguel Mendes
INTRODUCTION: Aortic stenosis is the most prevalent type of valvular disease in Europe. Surgical aortic valve replacement (SAVR) is the standard therapy, while transcatheter aortic valve implantation (TAVI) is an alternative in patients at unacceptably high surgical risk. Assessment by a heart team is recommended by the guidelines but there is little published evidence on this subject. The purpose of this paper is to describe the experience of a multidisciplinary TAVI program that began in 2008...
November 15, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/29153516/determination-of-lactadherin-concentration-in-dairy-by-products-by-elisa-effect-of-heat-treatment-and-hydrolysis
#17
Daniel Ripollés, José A Parrón, Javier Fraguas, Miguel Calvo, María D Pérez, Lourdes Sánchez
Lactadherin is a peripheral glycoprotein of the milk fat globule membrane with several attributed biological activities. In this study, we developed an indirect competitive ELISA to determine lactadherin concentration by using a rabbit polyclonal antiserum. The ELISA was applied to quantify lactadherin in several dairy by-products. Of the products tested, raw and commercial buttermilk had the highest concentrations of lactadherin (6.79 and 5.27 mg/g of product, respectively), followed by commercial butter serum (4...
November 15, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29153249/accurate-surgical-skills-evaluation-does-it-mandate-raters-have-a-medical-background
#18
Muhammad Zeb, Apram Jyot, Eduardo Abbott, Miguel Gomez, Mohamed Baloul, David Farley
BACKGROUND: Surgeons rarely have time to assess/rate trainee performance. From a 10 year-experience of implementing OSCE style assessments, we hypothesize that the accurate scoring of interns in selected tests is not affected by the rater's medical background. METHODS: A prospective collection of quantitative scoring data by both medical school graduates and college students was compared. Each rater underwent training and then watched three videos of actors performing in each of two OSCE stations and individually scored them...
November 11, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/29152988/value-and-innovation-of-direct-acting-antivirals-long-term-health-outcomes-of-the-strategic-plan-for-the-management-of-hepatitis-c-in-spain
#19
Juan Turnes, Raquel Domínguez-Hernández, Miguel Ángel Casado
OBJECTIVE: To assess the long-term healthcare costs and health outcome in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain. METHODS: A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAA, following SPCHC approval...
November 20, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29152874/concordance-and-correlation-of-activity-indices-in-patients-with-rheumatoid-arthritis-in-northwestern-colombia-a-cross-sectional-study
#20
Ricardo Restrepo-Correa, Libia M Rodríguez-Padilla, Aura L Zapata-Castellanos, Andrea Ocampo, Juan J García, Carolina Muñoz-Grajales, Luis F Pinto-Peñaranda, Javier D Márquez-Hernández, Miguel A Mesa-Navas, Carlos J Velásquez-Franco
AIM: To determine the correlation and concordance between different clinimetric scores in patients with rheumatoid arthritis in two high-complexity reference centers in northwestern Colombia. METHOD: A cross-sectional study in adults diagnosed with rheumatoid arthritis was conducted according to the 2010 American College of Rheumatology and European League Against Rheumatism Classification Criteria, between January and June, 2013. The correlation was evaluated using Spearman's correlation coefficient, and concordance with quadratic weighted kappa with the respective confidence intervals, for which patients were classified into different categories of disease activity...
November 19, 2017: International Journal of Rheumatic Diseases
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