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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/29458200/influence-of-treatment-modality-on-morbidity-and-mortality-in-periprosthetic-femoral-fracture-a-comparative-study-of-71-fractures-treated-by-internal-fixation-or-femoral-implant-revision
#2
S Cohen, X Flecher, S Parratte, M Ollivier, J N Argenson
INTRODUCTION: The incidence of periprosthetic femoral fracture is constantly increasing, with high associated morbidity and mortality. Surgical treatment is guided by the Vancouver classification, but the influence of type of treatment on morbidity and mortality has been little analyzed. The theoretic advantage of implant revision over internal fixation is that it should allow earlier weight-bearing, although the impact of this on morbidity and mortality and autonomy has not been demonstrated...
February 16, 2018: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/29458197/changes-in-motor-function-cognition-and-emotion-related-behavior-after-right-hemispheric-intracerebral-hemorrhage-in-various-brain-regions-of-mouse
#3
Wei Zhu, Yufeng Gao, Jieru Wan, Xi Lan, Xiaoning Han, Shanshan Zhu, Weidong Zang, Xuemei Chen, Wendy Ziai, Daniel F Hanley, Scott J Russo, Ricardo E Jorge, Jian Wang
Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458193/attenuation-of-neuro-inflammation-improves-survival-and-neurodegeneration-in-a-mouse-model-of-severe-neonatal-hyperbilirubinemia
#4
Simone Vodret, Giulia Bortolussi, Alessandra Iaconcig, Elena Martinelli, Claudio Tiribelli, Andrés F Muro
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458162/consumption-and-exposure-assessment-to-sunscreen-products-a-key-point-for-safety-assessment
#5
Marie-Pierre Gomez-Berrada, Anne-Sophie Ficheux, Sandrine Rakotomalala, Sonia Guillou, Murièle Bellec, Dominique De Javel, Alain-Claude Roudot, Pierre-Jacques Ferret
No abstract text is available yet for this article.
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458124/tryptophan-mediated-dimerization-of-the-tssl-transmembrane-anchor-is-required-for-type-vi-secretion-system-activity
#6
Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre P España, Laure Journet, Françoise Guerlesquin, Eric Cascales
The Type VI secretion system (T6SS) is a multiprotein complex used by bacteria to deliver effectors into target cells. The T6SS comprises a bacteriophage-like contractile tail structure anchored to the cell envelope by a membrane complex constituted of the TssJ outer membrane lipoprotein and the TssL and TssM inner membrane proteins. TssJ establishes contact with the periplasmic domain of TssM whereas the transmembrane segments of TssM and its cytoplasmic domain interact with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal transmembrane helix (TMH)...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458104/a-new-l-glutaminase-from-streptomyces-pratensis-nrc-10-gene-identification-enzyme-purification-and-characterization
#7
Sanaa E Tork, Magda M Aly, Omar Elsemin
In the current study, the purified l-glutaminase from Streptomyces pratensis NRC10 (GenBank number KC857622) was characterized. Its molecular weight was estimated to be 46 kDa and isoelectric point 7.4. Its Vmax was calculated to be 2.19 U/mg/min, while Km was 0.175 mM. The optimum pH and temperature were 9 and 45 °C, respectively. It was thermostable at 45 °C but thermally inactivated at 60 °C after 50 min. Moreover, its enzymatic activity was enhanced by K+ ions and inhibited by Mg2+ , Cu2+ , Ag+ , Hg2+ , Ni2+ , Fe2+ , Cr2 , Na+ , Ca2+ , and EDTA...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458095/rapid-loop-mediated-isothermal-amplification-detection-of-coeliac-disease-risk-alleles
#8
Michael Erlichster, Jason A Tye-Din, Michael D Varney, Efstratios Skafidas, Patrick Kwan
Human leukocyte antigen (HLA) genotyping has become a useful investigation in the diagnostic work-up of coeliac disease (CD), with utility in risk stratification and screening. However, broad application of this technology has been hindered by the cost and time burden of conventional laboratory-based assays. We have developed and validated CD-loop-mediated isothermal amplification (CD-LAMP), a LAMP assay, which enables rapid identification of the signature CD risk genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05...
February 16, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29458085/the-effect-of-surface-charge-and-ph-on-the-physiological-behaviour-of-cobalt-copper-manganese-antimony-zinc-and-titanium-oxide-nanoparticles-in-vitro
#9
Tiina Titma
The precise knowledge on various interactions of metal nanoparticles (NP) in a living organism is scarce. It is expected that metals can bind to nucleic acids, peptides and proteins (e.g. enzymes), and modify the functioning of vital cellular compartments after entering the organism. The predictive factors for quantitative nanostructure-activity relationship (QNAR) analysis could enhance efficient and harmless usage of nanoparticles (NPs) in the industry as well in the medicine. The studies value the composition of the NP corona determined by time, temperature and source of protein which has been found to implicate the physiological behaviour of NPs...
February 16, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29458037/distinguishing-keratoconic-eyes-and-healthy-eyes-using-ultrahigh-resolution-uhr-oct-based-corneal-epithelium-thickness-mapping
#10
Niklas Pircher, Florian Schwarzhans, Stephan Holzer, Jan Lammer, Doreen Schmidl, Ahmed M Bata, Renè M Werkmeister, Gerald Seidel, Gerhard Garhöfer, Andreas Gschließer, Leopold Schmetterer, Gerald Schmidinger
PURPOSE: Discovering new predictive parameters in the diagnostics of Keratoconus (KC) has high priority. Aim of this trial was to find differences in epithelial thickness (ET) maps of eyes with KC and healthy eyes. DESIGN: Institutional cross-sectional study. METHODS: In this study 40 keratoconic eyes and 76 healthy eyes were scanned using a custom-built ultrahigh resolution OCT. Automated segmentation ET-maps with 17 subsectors were calculated (central, temporal inferior, temporal superior, nasal inferior and nasal superior area)...
February 16, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29458028/are-portable-stereophotogrammetric-devices-reliable-in-facial-imaging-a-validation-study-of-vectra-h1-device
#11
Daniele Gibelli, Valentina Pucciarelli, Annalisa Cappella, Claudia Dolci, Chiarella Sforza
PURPOSE: Modern 3-dimensional (3D) image acquisition systems represent a crucial technologic development in facial anatomy because of their accuracy and precision. The recently introduced portable devices can improve facial databases by increasing the number of applications. In the present study, the VECTRA H1 portable stereophotogrammetric device was validated to verify its applicability to 3D facial analysis. MATERIALS AND METHODS: Fifty volunteers underwent 4 facial scans using portable VECTRA H1 and static VECTRA M3 devices (2 for each instrument)...
January 31, 2018: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29457997/detection-of-acute-and-long-term-effects-of-concussion-dual-task-gait-balance-control-vs-computerized-neurocognitive-test
#12
David R Howell, Louis R Osternig, Li-Shan Chou
OBJECTIVE: Our aim was to examine the acute (within 72 hours of injury) and long-term (2 months post-injury) independent associations between objective dual-task gait balance and neurocognitive measurements among adolescents and young adults with a concussion and matched controls. DESIGN: Longitudinal case-control SETTING: Motion analysis laboratory PARTICIPANTS: Participants who sustained a concussion underwent a dual-task gait analysis and computerized neurocognitive testing within 72 hours of injury and again 2 months later...
February 16, 2018: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/29457996/the-tyg-index-cutoff-point-and-its-association-with-body-adiposity-and-lifestyle-in-children
#13
Sarah A Vieira Ribeiro, Poliana C A Fonseca, Cristiana S Andreoli, Andréia Q Ribeiro, Helen H M Hermsdorff, Patrícia F Pereira, Silvia E Priore, Sylvia C C Franceschini
OBJECTIVE: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of IR in this population. METHODS: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat...
February 16, 2018: Jornal de Pediatria
https://www.readbyqxmd.com/read/29457934/early-placement-of-dental-implants-in-maxillary-sinus-grafted-with-leukocyte-and-platelet-rich-fibrin-l-prf-and-deproteinized-bovine-bone-mineral
#14
Elton Carlos Pichotano, Rafael Scaf de Molon, Luiz Guilherme Freitas de Paula, Ricardo Violante de Souza, Elcio Marcantonio, Daniela Leal Zandim-Barcelos
This case report aimed to describe the effects of leukocyte and platelet-rich fibrin (L-PRF) associated with deproteinized bovine bone mineral (DBBM) and absorbable collagen membrane (CM) on bone regeneration in maxillary sinus augmentation. A 59-year-old male patient was referred to the Department of Periodontology for implant rehabilitation of his edentulous upper jaw. The treatment plan involved maxillary sinus augmentation followed by implants installation. A split-mouth design was employed, in which the right maxillary sinus was filled using L-PRF, DBBM, and CM; the left side was filled with DBBM and CM...
February 19, 2018: Journal of Oral Implantology
https://www.readbyqxmd.com/read/29457923/flipping-social-determinants-on-its-head-medical-student-perspectives-on-the-flipped-classroom-and-simulated-patients-to-teach-social-determinants-of-health
#15
N Gostelow, J Barber, F Gishen, A Berlin
BACKGROUND: Inequalities in healthcare are increasing. Engaging medical students to tackle this urgent challenge alongside clinical sciences can be demanding. This study examines medical student perceptions of a flipped approach to health inequalities co-designed by faculty and sixth-year students. INNOVATION: A flipped learning session was piloted for year 4 medical students combining an online lesson followed by a tutorial with a simulated patient. METHODS: A mixed-methods approach collected questionnaire data using 4-point Likert scales and free text answers...
February 19, 2018: Medical Teacher
https://www.readbyqxmd.com/read/29457890/headspace-solid-phase-microextraction-coupled-to-miniaturized-microplasma-optical-emission-spectrometry-for-detection-of-mercury-and-lead
#16
Chengbin Zheng, Ligang Hu, Xiandeng Hou, Bin He, Guibin Jiang
Despite increased interest in microplasma atomic spectrometry over the past several years, its applications to field analysis of real samples still remain limited due to its low sensitivity. In this work, headspace solid-phase microextraction (HS-SPME) using PDMS/DVB fiber was used as a sample introduction method to improve the sensitivity of a miniature (6.0 cm length × 5.0 cm width × 2.8 cm height) low power (<10 W) microplasma point discharge optical emission spectrometer (PD-OES) for the determination of Hg and Pb after their derivatization with sodium tetraethylborate (NaBEt4)...
February 19, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29457876/pharmacokinetics-of-metformin-in-patients-with-gastrointestinal-intolerance
#17
L McCreight, T B Stage, P Connelly, M Lonergan, F Nielsen, C Prehn, J Adamski, K Brosen, E R Pearson
AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457837/improved-wound-remodeling-correlates-with-modulated-tgf-beta-expression-in-skin-diabetic-wounds-following-combined-red-and-infrared-photobiomodulation-treatments
#18
Reza Fekrazad, Arash Sarrafzadeh, Katayoun Am Kalhori, Imran Khan, Praveen R Arany, Alessio Giubellino
Diabetic wounds are a major cause of morbidity among patients with poorly controlled blood glucose levels. Conventional empirical wound care strategies have shown limited efficacy and there is an urgent need to develop novel therapeutic strategies. Photobiomodulation treatments have shown a positive therapeutic effects in several cell culture and animal models. In this study, we examined wound healing in diabetic rats following treatments with two laser wavelengths, namely red (660nm) and infrared (808nm) individually and in combination as compared to routine wound dressings...
February 19, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29457817/electron-transfer-rate-analysis-of-a-site-specifically-wired-copper-oxidase
#19
Orr Schlesinger, Mor Pasi, Rambabu Dandela, Michael M Meijler, Lital Alfonta
Electron transfer kinetic parameters of site-specifically wired copper oxidase were investigated. The enzyme's orientation towards the electrode was controlled by incorporation of propargyl-l-lysine as a site-specific anchoring point. Herein, we demonstrate the importance of immobilization orientation and how it affects electron transfer efficiency and kinetics to each of the enzyme's two active sites.
February 19, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29457796/h3b-8800-an-orally-available-small-molecule-splicing-modulator-induces-lethality-in-spliceosome-mutant-cancers
#20
Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith, Silvia Buonamici
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells...
February 19, 2018: Nature Medicine
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