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High tolerance

Peter Sandner, Peter Berger, Christoph Zenzmaier
Fibrotic diseases cause high rates of morbidity and mortality, and their incidence increases with age. Despite intense research and development efforts, effective and well-tolerated antifibrotic treatments are scarce. Transforming growth factor-β signaling, which is widely considered the most important profibrotic factor, causes a pro-oxidant shift in redox homeostasis and a concomitant decrease in nitric oxide (NO) signaling. The NO/cyclic guanosine monophosphate (cGMP) signaling cascade plays a pivotal role in the regulation of cell and organ function in whole-body hemostasis...
October 27, 2016: Gerontology
Charles Dalcanale Tesser, Armando Henrique Norman
This article contends that the distinction between clinical care (illness) and prevention of future disease is essential to the practice of quaternary prevention. The authors argue that the ongoing entanglement of clinical care and prevention transforms healthy into "sick" people through changes in disease classification criteria and/or cut-off points for defining high-risk states. This diverts health care resources away from those in need of care and increases the risk of iatrogenic harm in healthy people...
October 20, 2016: Cadernos de Saúde Pública
Michael Pieroni, Clara Lagomarsini, Danilo De Rossi, Federico Carpi
Electrically tunable lenses are conceived as deformable adaptive optical components able to change focus without motor-controlled translations of stiff lenses. In order to achieve large tuning ranges, large deformations are needed. This requires new technologies for the actuation of highly stretchable lenses. This paper presents a configuration to obtain compact tunable lenses entirely made of soft solid matter (elastomers). This was achieved by combining the advantages of dielectric elastomer actuation (DEA) with a design inspired by the accommodation of reptiles and birds...
October 26, 2016: Bioinspiration & Biomimetics
Rajeswaran Jagadeesan, Manoj K Nayak
BACKGROUND: Susceptibility to phosphine (PH3 ) and sulfuryl fluoride (SF) and cross resistance to SF were evaluated in two life stages (eggs and adults) of key grain insect pests, Rhyzopertha dominca (F.), Sitophilus oryzae (L.), Cryptolestes ferrugineus (Stephens), and Tribolium castaneum (Herbst). This study was performed with an aim to integrate SF into phosphine resistance management program in Australia. RESULTS: Characterisation of susceptibility and resistance to phosphine in eggs and adults showed that C...
October 26, 2016: Pest Management Science
Chandrashekhar V Kulkarni, Anan Yaghmur, Miloš Steinhart, Manfred Kriechbaum, Michael Rappolt
We present the first report on the effect of hydrostatic pressure on colloidally stabilized lipid nanoparticles enveloping inverse non-lamellar self-assemblies in their interiors. These internal self-assemblies were systematically tuned into bicontinuous cubic (Pn3m and Im3m), micellar cubic (Fd3m), hexagonal (H2), and inverse micellar (L2) phases by regulating the lipid-oil ratio while the hydrostatic pressure was varied from atmospheric pressure to 1200 bar, and back to the atmospheric pressure. The pressure effect on these lipid nanoparticles was compared with their equilibrium bulk, non-dispersed counterparts, i...
October 26, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Mengjun Tang, Xiaowen Sun, Shan Zhang, Juan Wan, Lin Li, Hong Ni
AIMS: The cell-surface display of chitinase Chi9602ΔSP was constructed on B. thuringiensis BMB171 by using two repeat N-terminal regions of autolysin (Mbgn)2 as the anchoring motif. This study aimed to prepare a chitinolytic whole-cell B. thuringiensis biocatalyst with improved catalytic and antifungal activities. METHODS AND RESULTS: The chitinase Chi9602ΔSP was displayed on the cell surface of B. thuringiensis BMB171 by using (Mbgn)2 as the anchoring motif. Immunofluorescence microscopic assays and flow cytometry confirmed that Chi9602ΔSP was anchored onto the surface of vegetative cells and spores...
October 26, 2016: Journal of Applied Microbiology
H-J Qiu, L Y Chen, Y Ito, J L Kang, X W Guo, P Liu, H Kashani, A Hirata, T Fujita, M W Chen
Graphene with a large specific surface area and high conductivity has a large specific capacitance. However, its volumetric capacitance is usually very low because the restacking of 2D graphene sheets leads to the loss of the large ion-accessible surface area. Here we report squeezable bicontinuous nanoporous nitrogen-doped graphene, which is extremely flexible and can tolerate large volume contraction by mechanical compression without the face-to-face restacking occurring. The compressed nanoporous N-doped graphene with a large ion accessible surface area and high conductivity shows an ultrahigh volumetric capacitance of ∼300 F cm(-3) together with excellent cycling stability and high rate performance...
October 26, 2016: Nanoscale
Liezel L Griffin, John T Lear
Non-melanoma skin cancer (NMSC) is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT) is gaining popularity for the treatment of basal cell carcinoma (BCC), Bowen's disease (BD) and actinic keratosis (AK). A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX) is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate) PDT for AKs has the advantage of decreased pain and better patient tolerance...
October 22, 2016: Cancers
Carlos Angulo Barrios
An optical link, based on a conventional Scotch tape waveguide, for sensing applications requiring rapid on-site assembly is proposed and demonstrated. The flexible waveguide contains an integrated aluminum one-dimensional grating coupler that, when stuck on the radiative surface of a light emitting device, allows light to be coupled in and transmitted through the tape, whose tip end is, in turn, adhered onto the photosensitive surface of a photodetector. The (de)coupling approaches exhibit high alignment tolerances that permit the formation of a free-standing flexible optical connection between surface-normal optoelectronic devices without the need of specialized equipment...
October 5, 2016: Sensors
Audrey H Lau, Matthew J Vitalone, Kelly Haas, Todd Shawler, Carlos O Esquivel, William E Berquist, Olivia M Martinez, Ricardo O Castillo, Sheri M Krams
Long-term IS in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. TOL, defined as graft acceptance without functional impairment in the absence of IS, has been achieved in some pediatric LT recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent IS. Single-cell mass cytometry was performed using blood samples from a single-center pediatric LT population of operationally tolerant patients to comprehensively characterize the immune cell populations in the tolerant state compared with patients on chronic low-dose IS...
October 26, 2016: Pediatric Transplantation
Kellie Toohey, Kate L Pumpa, Leonard Arnolda, Julie Cooke, Desmond Yip, Paul S Craft, Stuart Semple
PURPOSE: The aim of this study was to evaluate the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular disease risk factors in cancer survivors. METHODS: Cancer survivors within 24 months post-diagnosis were randomly assigned into the low-volume high-intensity interval training group (n = 8) or the continuous low to moderate intensity training group (n = 8) group for 36 sessions (12 weeks) of supervised exercise...
2016: PeerJ
Thomas Vercruysse, Jolien De Bie, Jasper Neggers, Maarten Jacquemyn, Els Vanstreels, Jonathan Leo Schmid-Burgk, Veit Hornung, Erkan Baloglu, Yosef Landesman, William Senapedis, Sharon Shacham, Antonis Dagklis, Jan Cools, Dirk Daelemans
PURPOSE: Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports many cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibition of XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained with the Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330) demonstrating activity in Phase-II/IIb clinical trials when dosed 1 - 3 times weekly. The second-generation SINE compound KPT-8602 shows improved tolerability and can be dosed daily...
October 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Dilfuza Egamberdieva, Stephan Wirth, Li Li, Elsayed Fathi Abd-Allah, Kristina Lindström
Liquorice (Glycyrrhiza uralensis Fisch.) is one of the most widely used plants in food production, and it can also be used as an herbal medicine or for reclamation of salt-affected soils. Under salt stress, inhibition of plant growth, nutrient acquisition and symbiotic interactions between the medicinal legume liquorice and rhizobia have been observed. We recently evaluated the interactions between rhizobia and root-colonizing Pseudomonas in liquorice grown in potting soil and observed increased plant biomass, nodule numbers and nitrogen content after combined inoculation compared to plants inoculated with Mesorhizobium alone...
October 26, 2016: Bioengineered
Lenneke Schrier, Rob Zuiker, Frans W H M Merkus, Erica S Klaassen, Zheng Guan, Bert Tuk, Joop M A van Gerven, Ronald van der Geest, Geert Jan Groeneveld
AIM: To evaluate the pharmacokinetics, pharmacodynamics, nasal tolerance and effects on sedation of a highly concentrated aqueous intranasal midazolam formulation (Nazolam) and to compare these to intravenous midazolam. METHODS: In this four-way crossover, double-blind, double-dummy, randomized, placebo-controlled study, 16 subjects received 2.5 mg Nazolam, 5.0 mg Nazolam, 2.5 mg intravenous midazolam or placebo on different occasions. Pharmacokinetics of midazolam and α-hydroxy-midazolam were characterized and related to outcome variables for sedation (Saccadic Peak Velocity, the Bond and Lader Visual Analogue Scale for sedation, the Simple Reaction Time Task and the Observer's Assessment of Alertness/Sedation)...
October 25, 2016: British Journal of Clinical Pharmacology
Jorge Regueiro, Noelia Negreira, Marc H G Berntssen
Ion mobility spectrometry allows for the measurement of the collision cross section (CCS), which provides information about the shape of an ionic molecule in the gas phase. While the hyphenation of travelling-wave ion mobility spectrometry (TWIMS) with high-resolution quadrupole time-of-flight mass spectrometry (QTOFMS) has been mainly used for structural elucidation purposes, its potential for fast screening of small molecules in complex samples has not yet been thoroughly evaluated. The current work explores the capabilities of ultra-high performance liquid chromatography (UHPLC) coupled to a new design TWIMS-QTOFMS for the screening and identification of a large set of pesticides in complex salmon feed matrices...
October 25, 2016: Analytical Chemistry
Lawrence Tim Goodnough, Josep Comin-Colet, Santiago Leal-Noval, Sherri Ozawa, Jacqueline Takere, David Henry, Mazyar Javidroozi, Benjamin Hohmuth, Elvira Bisbe, Irwin Gross, Aryeh Shander
Anemia is an independent risk factor for adverse patient outcomes. There are no guidelines for management of anemia in patients withcongestive heart failure (CHF), despite itshigh incidence. Four objectives were defined by the International Anemia Management and Clinical Outcomes Expert Panel (AMCO), a multinational group of interdisciplinary experts identified by the Society for the Advancement of Blood Management (SABM) to: determine the prevalence of anemia in outpatients; to determine the prevalence of hospital-acquired anemia; to assess the impact of anemia management on clinical outcomes such as quality of life and functional status; and to provide recommendations for primary care physicians and specialists for the diagnosis, evaluation, and management of anemia in patients with CHF...
October 25, 2016: American Journal of Hematology
Da Hae Lee, Bart Keymeulen, Robert Hilbrands, Zhidong Ling, Ursule Van de Velde, Daniel Jacobs-Tulleneers-Thevissen, Geert Maleux, Bruno Lapauw, Laurent Crenier, Christophe De Block, Chantal Mathieu, Daniel Pipeleers, Pieter Gillard
BACKGROUND: Induction therapy with a T cell depleting agent followed by mycophenolate mofetil (MMF) and tacrolimus (Tac) is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. METHODS: Fifty-one patients (ages between 29-63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin (ATG)-MMF-Tac protocol...
October 25, 2016: Transplantation
Patrizia Bonadonna, Massimiliano Bonifacio, Roberta Zanotti
Mastocytosis is a clonal disease characterized by proliferation and accumulation of mast cells (MC) in different tissues, preferentially skin and bone marrow, leading to a wide variety of clinical manifestations, mainly caused by the inappropriate release of MC mediators. As a consequence, patients with mastocytosis may experience symptoms due to massive MC activation and release of mediators. Anaphylaxis is the most frequent manifestation of this phenomenon.Drugs are possible triggers of anaphylaxis in patients with mastocytosis, even though the association between mastocytosis and drug anaphylaxis does not appear to be as strong as anaphylaxis after hymenoptera sting; nevertheless, MC disorders might be ruled out in cases of severe systemic reactions to drugs...
September 28, 2016: Current Pharmaceutical Design
Amy C Arnold, Emily M Garland, Jorge E Celedonio, Satish R Raj, Naji N Abumrad, Italo Biaggioni, David Robertson, James M Luther, Cyndya A Shibao
CONTEXT: Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine into norepinephrine. These patients have absence of sympathetic adrenergic function, predisposing to orthostatic hypotension. DBH deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. CASE DESCRIPTION: We describe the metabolic profile of an adolescent female DBH deficient patient...
October 25, 2016: Journal of Clinical Endocrinology and Metabolism
Artur K Mailyan, Kyle Young, Joanna L Chen, Bradley T Reid, Armen Zakarian
A method for a directed stereoselective guanidinylation of alkenes is described. The guanidine unit can be delivered as an intact fragment by a hydroxy or carboxy group, usually with a high level of stereocontrol. After the guanidine delivery, the directing group can be cleaved under exceptionally mild conditions, typically by alcoholysis in the presence of acetic acid. Broad functional group tolerance and mild reaction conditions for the cycloguanidilation suggest applications in medicinal chemistry and natural products synthesis...
October 25, 2016: Organic Letters
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