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https://www.readbyqxmd.com/read/28647917/novel-endpoints-for-heart-failure-clinical-trials
#1
REVIEW
Carine E Hamo, Mihai Gheorghiade, Javed Butler
PURPOSE OF REVIEW: With the growing prevalence of heart failure, there is a particular need to develop new pharmacologic treatments that can improve outcomes. While there are several approved therapies for heart failure with reduced ejection fraction, there is currently no approved agent for those with preserved ejection fraction. The current review aimed to explore the utility of alternate endpoints to mortality and hospitalization. RECENT FINDINGS: There is increased interest in the use of alternative endpoints such as functional status and quality of life for heart failure drug development to focus on patients feeling better in addition to improving outcomes...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28647474/antiviral-profiling-of-the-capsid-assembly-modulator-bay41-4109-on-full-length-hbv-genotype-a-h-clinical-isolates-and-core-site-directed-mutants-in-vitro
#2
Jan Martin Berke, Ying Tan, Thierry Verbinnen, Pascale Dehertogh, Karen Vergauwen, Ann Vos, Oliver Lenz, Frederik Pauwels
The HBV core protein represents an attractive target for new antiviral therapies due to its multiple functions within the viral life-cycle. Here, we report the antiviral activity of the capsid assembly modulator (CAM) BAY41-4109 and two nucleos(t)ide analogues (NAs) on a diverse panel of 54 HBV clinical isolates from genotype (GT) A-H and assessed the impact of core amino acid (aa) substitutions using site-directed mutants (SDMs). The median EC50 values of BAY41-4109 across genotypes ranged from 26 nM in GT G to 215 nM in GT F irrespective of the presence of NA resistance mutations compared to 43 nM for the GT D reference construct...
June 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28647443/dermal-and-transdermal-delivery-of-pharmaceutically-relevant-macromolecules
#3
REVIEW
S Münch, J Wohlrab, R H H Neubert
The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin...
June 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28647358/mitochondria-associated-membranes-mams-an-emerging-platform-connecting-energy-and-immune-sensing-to-metabolic-flexibility
#4
Jennifer Rieusset
Living organisms have the capacity to sense both nutrients and immune signals in order to adapt their metabolism to the needs, and both metabolic inflexibility and exacerbated immune responses are associated with metabolic diseases. Over the past decade, mitochondria emerged as key nutrient and immune sensors regulating numerous signalling pathways, and mitochondria dysfunction has been extensively implicated in metabolic diseases. Interestingly, mitochondria interact physically and functionally with the endoplasmic reticulum (ER, in contact sites named mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium and regulate cellular homeostasis...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647351/development-of-an-on-off-switchable-fluorescent-probe-targeting-his-tag-fused-proteins-in-living-cells
#5
Koyo Okitsu, Takashi Misawa, Takuji Shoda, Masaaki Kurihara, Yosuke Demizu
The fluorescent labeling of target proteins is useful for analyzing their functions and localization in cells, and several fluorescent probes have been developed. However, the fusion of tags such as green fluorescent protein (GFP) to target proteins occasionally affects their functions and/or localization in living cells. Therefore, an imaging method that uses short peptide tags such as hexa-histidine (the His tag) has been attracting increasing attention. Few studies have investigated ON/OFF switchable fluorescent probes for intracellular His-tagged proteins...
May 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28647242/effect-of-oxide-nanoparticles-on-the-morphology-and-fluidity-of-phospholipid-membranes-and-the-role-of-hydrogen-bonds
#6
Xiaoran Wei, Junchao Yu, Lei Ding, Jingtian Hu, Wei Jiang
Engineered oxide nanoparticles (NPs) are widely applied in insulators, catalyzers, paints, cosmetic products, textiles and semiconductors. Their attachment on cell membrane may lead to cytotoxicity. The effects of Al2O3, Fe2O3, SiO2, TiO2 and ZnO NPs on membrane integrity and fluidity were studied using giant or small unilamellar vesicles in this study. Al2O3 and SiO2 NPs disrupted the oppositely charged membrane, indicating the important role of electrostatic attraction. However, Fe2O3, TiO2 and ZnO NPs did not cause serious membrane disruption as Al2O3 and SiO2 NPs...
July 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28647144/simultaneous-determination-of-uv-filters-and-estrogens-in-aquatic-invertebrates-by-modified-quick-easy-cheap-effective-rugged-and-safe-extraction-and-liquid-chromatography-tandem-mass-spectrometry
#7
Ke He, Anne Timm, Lee Blaney
Ultraviolet-filters (UV-filters) and estrogens have attracted increased attention as contaminants of emerging concern (CECs) due to their widespread occurrence in the environment. Most of these CECs are hydrophobic and have the potential to accumulate in aquatic organisms. To date, co-analysis of UV-filters and estrogens has not been reported due, in part, to the complex environmental matrices. Here, a multi-residue method has been developed for simultaneous determination of five UV-filters and three estrogens in tissue from aquatic and marine organisms...
June 15, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28647127/infrared-light-detection-by-the-haller-s-organ-of-adult-american-dog-ticks-dermacentor-variabilis-ixodida-ixodidae
#8
Robert D Mitchell, Jiwei Zhu, Ann L Carr, Anirudh Dhammi, Grayson Cave, Daniel E Sonenshine, R Michael Roe
The Haller's organ (HO), unique to ticks and mites, is found only on the first tarsus of the front pair of legs. The organ has an unusual morphology consisting of an anterior pit (AP) with protruding sensilla and a posterior capsule (Cp). The current thinking is that the HO's main function is chemosensation analogous to the insect antennae, but the functionality of its atypical structure (exclusive to the Acari) is unexplained. We provide the first evidence that the HO allows the American dog tick, Dermacentor variabilis, to respond to infrared (IR) light...
June 13, 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/28646962/the-long-shadow-of-lemierre-s-syndrome
#9
Joshua Osowicki, Sarah Kapur, Linny Kimly Phuong, Simon Dobson
Lemierre's syndrome is a rare and feared complication of pharyngitis, occurring most commonly in adolescents and young adults. It is typically defined by the constellation of septic internal jugular vein thrombophlebitis, pulmonary and other septic emboli, and sterilesite infection by Fusobacterium necrophorum. The rarity and severity of Lemierre's syndrome has made it an attractive subject for case reports but there is a paucity of evidence to inform areas of persistent uncertainty. In recent years, heightened attention and controversy has focused upon speculation that a purported rise in the incidence of Lemierre's syndrome is due to reduced antibiotic prescribing for respiratory tract infections, that F...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28646882/magnetic-foreign-body-ingestion-in-pediatric-patients-report-of-three-cases
#10
Jinbeom Cho, Kiyoung Sung, Dosang Lee
BACKGROUND: Although foreign bodies (FBs) typically pass spontaneously and uneventfully through the digestive tract, a subset of such bodies may become trapped, eventually leading to significant injury. In particular, the ingestion of magnetic materials can cause serious morbidity due to proximate attraction through the intestinal wall. CASE PRESENTATION: We recently treated three pediatric patients who had ingested several magnetic foreign materials. None of these patients exhibited any clinical symptoms or signs suggestive of surgical abdomen...
June 24, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28646881/heme-molecule-functions-as-an-endogenous-agonist-of-astrocyte-tlr2-to-contribute-to-secondary-brain-damage-after-intracerebral-hemorrhage
#11
Hyunjung Min, Boomin Choi, Yong Ho Jang, Ik-Hyun Cho, Sung Joong Lee
Toll-like receptor 2 (TLR2) was recently shown to contribute to secondary brain damage after intracerebral hemorrhage (ICH), although the molecular mechanisms of this contribution are elusive. In this study, we tested the hypothesis that hemin functions as a TLR2 endogenous agonist, causing proinflammatory astrocyte activation and secondary brain damage after ICH. Hemin administration to the mouse brain striatum induced ICH injury and neurological deficits, however, the brain injury volume and neurological deficits due to hemin injection were significantly reduced in TLR2 knock-out (KO) mice...
June 24, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28646833/the-use-of-fruit-extracts-for-production-of-apple-chips-with-enhanced-antioxidant-activity
#12
Tomasz Tarko, Aleksandra Duda-Chodak, Dorota Semik-Szczurak
Background: Style and pace of life make consumers more willing to reach for snack products. This group of processed food includes, among others, fruit chips. Due to the increasing incidence of diseases associated with the excessive exposure to free radicals foods enriched with antioxidant compounds, eg. polyphenols, can be introduced into the sale. Objective: The aim of the study was to use the fruit extracts for the production of apple chips with enhanced antioxidant activity...
2017: Roczniki Państwowego Zakładu Higieny
https://www.readbyqxmd.com/read/28646729/the-structure-of-ptsd-symptoms-according-to-dsm-5-and-idc-11-proposal-a-multi-sample-analysis
#13
M Cyniak-Cieciura, K Staniaszek, A Popiel, E Pragłowska, B Zawadzki
Posttraumatic stress disorder (PTSD) symptoms structure is a subject of ongoing debate since its inclusion in DSM-III classification in 1980. Different research on PTSD symptoms structure proved the better fit of four-factor and five-factor models comparing to the one proposed by DSM-IV. With the publication of DSM-5 classification, which introduced significant changes to PTSD diagnosis, the question arises about the adequacy of the proposed criteria to the real structure of disorder symptoms. Recent analyses suggest that seven-factor hybrid model is the best reflection of symptoms structure proposed to date...
May 4, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28646556/injury-induced-maladaption-and-dysregulation-of-calcium-channel-alpha-2-delta-subunit-proteins-and-its-contribution-to-neuropathic-pain-development
#14
REVIEW
Nian Gong, John Park, Z David Luo
Voltage gated calcium channels (VGCCs) play important roles in physiological functions including modulations of neurotransmitter release, neuronal network activities, intracellular signaling pathways, and gene expression. Some pathological conditions, including nerve injuries, can cause dysregulation of VGCCs and their subunits. This in turn can lead to functional maladaption of VGCCs and their subunits, which can contribute to development of disorders such as pain sensations. This review summarized recent findings related to maladaptive changes of dysregulated VGCC alpha-2-delta-1 subunit (Cav α2 δ1 ) with a focus on exploration of mechanisms underlying contribution of Cav α2 δ1 to pain signal transduction...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#15
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646417/mesenchymal-stem-cell-therapy-for-acute-and-chronic-pancreatitis
#16
REVIEW
Kazumichi Kawakubo, Shunsuke Ohnishi, Masaki Kuwatani, Naoya Sakamoto
Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various gastrointestinal diseases, such as graft-versus-host disease, inflammatory bowel disease, and liver cirrhosis. Therefore, MSC therapy has the potential to be a novel treatment for acute and chronic pancreatitis by suppressing inflammation. Several studies have investigated the effect of MSC therapy on acute and chronic pancreatitis, but the underlying mechanisms remain unknown...
June 23, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28646369/impacts-of-a-temporary-urban-pop-up-park-on-physical-activity-and-other-individual-and-community-level-outcomes
#17
Deborah Salvo, Jorge A Banda, Jylana L Sheats, Sandra J Winter, Daniela Lopes Dos Santos, Abby C King
Physical inactivity is a known risk factor for obesity and a number of chronic diseases. Modifying the physical features of neighborhoods to provide residents with equitable and convenient access to spaces for physical activity (PA) is a promising strategy for promoting PA. Public urban recreation spaces (e.g., parks) play an important role in promoting PA and are potentially an important neighborhood element for optimizing social capital and liveability in cities. Most studies examining the effects of park availability and use on PA have focused on traditional, permanent parks...
June 23, 2017: Journal of Urban Health: Bulletin of the New York Academy of Medicine
https://www.readbyqxmd.com/read/28646157/current-induced-resistive-state-in-fe-se-te-superconducting-nanostrips
#18
Ciro Nappi, Carlo Camerlingo, Emanuele Enrico, Emilio Bellingeri, Valeria Braccini, Carlo Ferdeghini, Ettore Sarnelli
We study the current-voltage characteristics of Fe(Se,Te) thin films deposited on CaF2 substrates in form of nanostrips (width w ~ λ, λ the London penetration length). In view of a possible application of these materials to superconductive electronics and micro-electronics we focus on transport properties in small magnetic field, the one generated by the bias current. From the characteristics taken at different temperatures we derive estimates for the pinning potential U and the pinning potential range δ for the magnetic flux lines (vortices)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646118/direct-oral-anticoagulants-for-treatment-of-hit-update-of-hamilton-experience-and-literature-review
#19
Theodore E Warkentin, Menaka Pai, Lori-Ann Linkins
Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, Canada, since January 1, 2015 (when we completed our prospective rivaroxaban for HIT study) using rivaroxaban for serologically-confirmed HIT (4Ts score ≥4 points, PF4/heparin immunoassay-positive, serotonin-release assay positive). We also performed a literature review of HIT treatment using a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28645921/the-east-asian-origin-of-the-giant-lobelias
#20
Eric B Knox, Chunjiao Li
PREMISE OF THE STUDY: Rapid radiations are difficult to reconstruct when organismal diversification and biogeographic movement outpace the evolution of genes typically used in phylogenetic analyses. The 125 kb of unique sequence from complete plastid genomes (= plastomes) largely solves the molecular sampling problem, and taxon sampling that triangulates the base of each major subclade largely solves the long-branch attraction problem. This combination of molecular and phylogenetic sampling is used to reconstruct the cosmopolitan radiation of lobeliads, with special focus on the origin of the giant lobelias...
June 2017: American Journal of Botany
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