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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29453205/co-deficiency-of-lysosomal-mucolipins-3-and-1-in-cochlear-hair-cells-diminishes-outer-hair-cell-longevity-and-accelerates-age-related-hearing-loss
#2
Teerawat Wiwatpanit, Natalie N Remis, Aisha Ahmad, Yingjie Zhou, John C Clancy, Mary Ann Cheatham, Jaime García-Añoveros
Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. While mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells -hair cells (HCs) and marginal cells of the stria vascularis- and very few other cell types...
February 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29449189/adjuvant-chemoradiotherapy-versus-radiotherapy-alone-for-women-with-high-risk-endometrial-cancer-portec-3-final-results-of-an-international-open-label-multicentre-randomised-phase-3-trial
#3
Stephanie M de Boer, Melanie E Powell, Linda Mileshkin, Dionyssios Katsaros, Paul Bessette, Christine Haie-Meder, Petronella B Ottevanger, Jonathan A Ledermann, Pearly Khaw, Alessandro Colombo, Anthony Fyles, Marie-Helene Baron, Ina M Jürgenliemk-Schulz, Henry C Kitchener, Hans W Nijman, Godfrey Wilson, Susan Brooks, Silvestro Carinelli, Diane Provencher, Chantal Hanzen, Ludy C H W Lutgens, Vincent T H B M Smit, Naveena Singh, Viet Do, Romerai D'Amico, Remi A Nout, Amanda Feeney, Karen W Verhoeven-Adema, Hein Putter, Carien L Creutzberg
BACKGROUND: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup...
February 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29448862/filgotinib-for-the-treatment-of-crohn-s-disease
#4
Remi Labetoulle, Stephane Paul, Xavier Roblin
Inflammatory Bowel Diseases, such as Crohn's disease (CD) and Ulcerative Colitis (UC), are widespread diseases (with an estimated 2.2 million Europeans affected), and even populations previously considered 'low risk' (such as Japan and India) are witnessing an increasing incidence. CD is a chronic, progressive immunologically driven disease, with an evolution characterized by succession of periods of progression and remission. New physiopathological pathways are continuously being discovered, the more we understand about how the disease appears and progresses, the more targets become available for the development of novel therapies...
February 15, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29443507/three-dimensional-directionality-is-a-pivotal-structural-feature-for-the-bioactivity-of-azabisphosphonate-capped-poly-phosphorhydrazone-nanodrug-dendrimers
#5
Myriam Hayder, Matteo Garzoni, Davide Bochicchio, Anne-Marie Caminade, François Couderc, Varravaddheay Ong-Meang, Jean-Luc Davignon, Cédric-Olivier Turrin, Giovanni M Pavan, Remy Poupot
Dendrimers are nanosized, non-linear, hyperbranched polymers whose overall three-dimensional shape is key for their biological activity. Poly(PhosphorHydrazone) (PPH) dendrimers capped with aza-bisphosphonate (ABP) end groups are known to have anti-inflammatory properties enabling the control of inflammatory diseases in different mouse models. Here we screen the anti-inflammatory activity of a series of PPH bearing between 2 and 16 ABP end groups in a mouse model of arthritis, and confront the biological results with atomistic simulations of the dendrimers...
February 14, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29439800/-occupational-health-in-china-an-emerging-issue
#6
Violaine Zhu, Cynthia Fleury, Cédric Denis-Rémis
In Chinese factories, the prevention of occupational illness is inadequate. Public authorities have only recently started to pay attention to the issue. Individual and collective protection measures need to be developed, employees made aware of the issues and controls improved.
January 2018: Soins; la Revue de Référence Infirmière
https://www.readbyqxmd.com/read/29438972/interference-of-hyperleukocytosis-in-red-blood-cell-count
#7
Rémy Favre, Alexis Genthon
No abstract text is available yet for this article.
February 8, 2018: Blood
https://www.readbyqxmd.com/read/29438322/the-application-of-nhej-crispr-cas9-and-cre-lox-system-in-the-generation-of-bivalent-duck-enteritis-virus-vaccine-against-avian-influenza-virus
#8
Pengxiang Chang, Yongxiu Yao, Na Tang, Jean-Remy Sadeyen, Joshua Sealy, Anabel Clements, Sushant Bhat, Muhammad Munir, Juliet E Bryant, Munir Iqbal
Duck-targeted vaccines to protect against avian influenza are critically needed to aid in influenza disease control efforts in regions where ducks are endemic for highly pathogenic avian influenza (HPAI). Duck enteritis virus (DEV) is a promising candidate viral vector for development of vaccines targeting ducks, owing to its large genome and narrow host range. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system is a versatile gene-editing tool that has proven beneficial for gene modification and construction of recombinant DNA viral vectored vaccines...
February 13, 2018: Viruses
https://www.readbyqxmd.com/read/29437443/proposal-for-a-quantum-test-of-the-weak-equivalence-principle-with-entangled-atomic-species
#9
Remi Geiger, Michael Trupke
We propose an experiment to test the weak equivalence principle (WEP) with a test mass consisting of two entangled atoms of different species. In the proposed experiment, a coherent measurement of the differential gravity acceleration between the two atomic species is considered, by entangling two atom interferometers operating on the two species. The entanglement between the two atoms is heralded at the initial beam splitter of the interferometers through the detection of a single photon emitted by either of the atoms, together with the impossibility of distinguishing which atom emitted the photon...
January 26, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29436616/synergistic-promoting-effects-of-pentoxifylline-and-simvastatin-on-the-apoptosis-of-triple-negative-mda-mb-231-breast-cancer-cells
#10
Yessica Cristina Castellanos-Esparza, Shuang Wu, Limin Huang, Catherine Buquet, Rong Shen, Berenice Sanchez-Gonzalez, Ethel Awilda García Latorre, Olivier Boyer, Remi Varin, Luis Antonio Jiménez-Zamudio, Anne Janin, Jean-Pierre Vannier, Hong Li, He Lu
Pentoxifylline (PTX), a xanthine family molecule and simvastatin (SIM), an anti-hypercholesterolemic agent, have recently been considered as sensitizers to chemotherapy and radiotherapy. The present in vitro study evaluated their antitumor synergistic effects on MDA‑MB‑231 breast cancer cells characterized by the triple‑negative phenotype (TNP). The anti-proliferative effects of these two agents were evaluated by MTT and clonogenic assays. Cell cycle progression was examined using propidium iodide staining...
February 9, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29436509/tracking-random-walks
#11
Riccardo Gallotti, Rémi Louf, Jean-Marc Luck, Marc Barthelemy
In empirical studies, trajectories of animals or individuals are sampled in space and time. Yet, it is unclear how sampling procedures bias the recorded data. Here, we consider the important case of movements that consist of alternating rests and moves of random durations and study how the estimate of their statistical properties is affected by the way we measure them. We first discuss the ideal case of a constant sampling interval and short-tailed distributions of rest and move durations, and provide an exact analytical calculation of the fraction of correctly sampled trajectories...
February 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29436287/which-assessment-method-of-malnutrition-in-head-and-neck-cancer
#12
Nicolas Saroul, Rémy Pastourel, Aurélien Mulliez, Nicolas Farigon, Vincent Dupuch, Thierry Mom, Yves Boirie, Laurent Gilain
Objective To assess the value of several diagnostic methods of nutritional status during the initial management of a head and neck cancer. Study Design Single-center prospective study. Setting Tertiary referral center. Subjects and Methods Ninety patients with head and neck cancer participated in the study. Assessment of their nutritional status was made with anthropometric, biological, body, and muscle measurements (the last by computed tomography: L3 muscle mass index [L3MMI]). Assessment of muscle performance (functional reflection of nutritional status) was made via the Short Physical Performance Battery test...
February 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29434608/a-case-of-type-2-hypersensitivity-to-rasburicase-diagnosed-with-a-natural-killer-cell-activation-assay
#13
Sébastien Viel, Rémi Pescarmona, Alexandre Belot, Audrey Nosbaum, Christine Lombard, Thierry Walzer, Frédéric Bérard
Drug hypersensitivity reactions can lead to different clinical pictures depending on the underlying immunological mechanism. Diagnosis tests are already available to assess the most frequent drugs hypersensitivity reactions, which are mediated by specific IgE or T cells. However, it remains challenging to diagnose type 2 hypersensitivity reactions (T2HR), which can lead to severe cytopenia and liver failure. Here, we describe a case of T2HR to rasburicase, an uricolytic agent used to prevent tumor lysis syndrome...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29429390/belgian-guidelines-for-non-occupational-hiv-post-exposure-prophylaxis-2017
#14
Agnès Libois, Eric Florence, Inge Derdelinckx, Jean Cyr Yombi, Sophie Henrard, Françoise Uurlings, Stefaan Vandecasteele, Sabine D Allard, Rémy Demeester, Filip Van Wanzeele, Nathalie Ausselet, Stéphane De Wit
We present the updated Belgian guidelines for the use of non-occupational HIV post-exposure prophylaxis (NONOPEP). This document is inspired by UK guidelines 2015, adapted to the Belgian situation and approved by all AIDS reference centers in Belgium. When recommended, NONOPEP should be initiated as soon as possible, preferably within 24 h of exposure but can be offered up to 72 h. The duration of NONOPEP should be 28 days. These current guidelines include epidemiologic estimations, which can be used to calculate the risk of infection after a potential exposure and help to decide whether or not to start prophylaxis...
February 12, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29425320/treatment-for-uncomplicated-plasmodium-falciparum-malaria-in-french-soldiers-deployed-in-sub-saharan-africa-gaps-between-policy-and-field-practice
#15
Anne Perisse, Guillaume Velut, Emilie Javelle, Gwion Loarer, Remy Michel, F Simon
Background: Malaria prevention and treatment are big challenges for the French forces deployed in sub-Saharan Africa. Since December 2013, 1,800 French soldiers have been deployed at any one time in the Central African Republic in the framework of "Operation Sangaris" and European Union Force (EUFOR). Over the 2014-2015 period, about 500 cases of malaria were notified in these troops during the operation or after their return (annual incidence: 13.4 p.100 person-year). The recommendation to use dihydroartemisinin-piperaquine (DHA-PQ) as the first-line treatment for French soldiers suffering from uncomplicated Plasmodium falciparum malaria in endemic areas is not always followed in practice in the field by French military general practitioners (GPs)...
February 7, 2018: Military Medicine
https://www.readbyqxmd.com/read/29425146/nanoparticle-based-strategies-to-treat-neuro-inflammation
#16
REVIEW
Rémy Poupot, Dylan Bergozza, Séverine Fruchon
Neuro-inflammation is a pivotal physio-pathological feature of brain disorders, including neurodegenerative diseases. As such, it is a relevant therapeutic target against which drugs have to be proposed. Targeting neuro-inflammation implies crossing the Blood-Brain Barrier (BBB) to reach the Central Nervous System (CNS). Engineered nanoparticles (ENPs) are promising candidates to carry and deliver drugs to the CNS by crossing the BBB. There are several strategies to design ENPs intended for crossing through the BBB...
February 9, 2018: Materials
https://www.readbyqxmd.com/read/29422651/impact-of-erroneous-meal-insulin-bolus-with-dual-hormone-artificial-pancreas-using-a-simplified-bolus-strategy-a-randomized-controlled-trial
#17
Véronique Gingras, Mohamed Raef Smaoui, Charlotte Cameli, Virginie Messier, Martin Ladouceur, Laurent Legault, Rémi Rabasa-Lhoret
Postprandial glucose control remains challenging for patients with type 1 diabetes (T1D). A simplified meal bolus approach with a dual-hormone (insulin and glucagon) closed-loop system (DH-CLS) has been tested; yet, the impact of categorization errors with this strategy is unknown. The objective was to compare, in a randomized controlled inpatient trial, DH-CLS with the simplified meal bolus approach for two different meals properly categorized or overestimated. We tested, in patients with T1D, the simplified strategy with two standardized breakfasts (n = 10 per meal) adequately categorized or overestimated: (1) 75 g and (2) 45 g of carbohydrate...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29422602/acidic-organelles-mediate-tgf-%C3%AE-1-induced-cellular-fibrosis-via-pro-renin-receptor-and-vacuolar-atpase-trafficking-in-human-peritoneal-mesothelial-cells
#18
Ikuko Oba-Yabana, Takefumi Mori, Chika Takahashi, Takuo Hirose, Yusuke Ohsaki, Satoshi Kinugasa, Yoshikazu Muroya, Emiko Sato, Geneviève Nguyen, Rémi Piedagnel, Pierre M Ronco, Kazuhito Totsune, Sadayoshi Ito
TGF-β1, which can cause renal tubular injury through a vacuolar-type H+-ATPase (V-ATPase)-mediated pathway, is induced by the glucose degradation product methylglyoxal to yield peritoneal injury and fibrosis. The present study investigated the roles of V-ATPase and its accessory protein, the (pro)renin receptor, in peritoneal fibrosis during peritoneal dialysis. Rats daily administered 20 mM methylglyoxal intraperitoneally developed significant peritoneal fibrosis after 7 days with increased expression of TGF-β and V-ATPase, which was reduced by the inhibition of V-ATPase with co-administration of 100 mM bafilomycin A1...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29421005/systematic-review-and-meta-analysis-of-endovascular-and-surgical-revascularization-for-patients-with-chronic-lower-extremity-venous-insufficiency-and-varicose-veins
#19
Sreekanth Vemulapalli, Kishan Parikh, Remy Coeytaux, Victor Hasselblad, Amanda McBroom, Abigail Johnston, Giselle Raitz, Matthew J Crowley, Kathryn R Lallinger, W Schuyler Jones, Gillian D Sanders
BACKGROUND: Chronic lower extremity venous disease (LECVD) is twice as prevalent as coronary heart disease, and invasive therapies to treat LECVD accounted for an estimated $290 million in Medicare expenditures in 2015. Despite increasing use of these invasive therapies, their comparative effectiveness is unknown. METHODS: We conducted a systematic review and meta-analysis of treatments for patients (symptomatic and asymptomatic) with lower extremity varicosities and/or lower extremity chronic venous insufficiency/incompetence/reflux...
February 2018: American Heart Journal
https://www.readbyqxmd.com/read/29416068/internal-noise-sources-limiting-contrast-sensitivity
#20
Daphné Silvestre, Angelo Arleo, Rémy Allard
Contrast sensitivity varies substantially as a function of spatial frequency and luminance intensity. The variation as a function of luminance intensity is well known and characterized by three laws that can be attributed to the impact of three internal noise sources: early spontaneous neural activity limiting contrast sensitivity at low luminance intensities (i.e. early noise responsible for the linear law), probabilistic photon absorption at intermediate luminance intensities (i.e. photon noise responsible for de Vries-Rose law) and late spontaneous neural activity at high luminance intensities (i...
February 7, 2018: Scientific Reports
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