Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a specified range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs

Composite Polymer Hydrogels with high and Reversible Elongation under Magnetic Stimuli

The field of soft actuators is dominated by elastomers that experience mechanical deformations in response to external stimuli. In this context, magnetic stimuli attract considerable interest because of their easy application, tunability, fast response, remote actuation, and safe penetration in biological environments. Since very recently, research interests in the field are being redirected towards hydrogels, which could virtually replace elastomers, overcoming their limitations and expanding the field of application of soft actuators. The mechanical actuation of hydrogels is a nascent field full of challenges, such as achieving reliable and significant responsiveness. Here we demonstrate that the combination of a physical polymer hydrogel with a dispersed phase consisting of clusters of magnetic particles, results in magnetic hydrogel composites that exhibit high and reversible elongation in response to magnetic stimuli. Our analyses show that this response is strongly dependent on the matrix elasticity, the concentration of magnetic particles, and the particle distribution within the network of polymer nanofibres. Our strategy for the maximization of the response of magnetic hydrogels should be a catalyst for the development of novel applications of composite hydrogels, such as a valve remotely actuated by a magnetic field that we also present here as a proof-of-concept. © 2021 The Author(s).Dr. Mariusz Barczak is acknowledged for help with SEM imaging of iron particles. Ms. Laura Quesada de la Torre is acknowledged for help with design of graphical abstract. This study was supported by project FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union ). CGV acknowledges financial support by Ministerio de Ciencia, Innovación y Universidades and University of Granada, Spain, for her FPU17/00491 grant. AZ thanks the Russian Science Foundation, project 20-12-00031, for the financial support. LRA thanks the Spanish State Research Agency (Spanish Ministry of Science and Innovation ) through Juan de la Cierva Incorporacion Fellowship ( IJC2018-037951-I ). Funding for open access charge: Universidad de Granada / CBUA

Dynamic and wear study of an extremely bidisperse magnetorheological fluid

Acceso a la versión publicada en Smart Mater. Struct. 24(12) 127001 (http://iopscience.iop.org/0964-1726/24/12/127001)"This is an author-created, un-copyedited version of an article accepted for publication/published in Smart Materials and Structures. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0964-1726/24/12/127001."In this work the friction and wear properties of five magnetorheologicalfluids (MRFs)with varying compositions are investigated. Considering that many of the proposed applications for these fluids involve lubricated contact between mobile metal –metal or polymer– metal parts, the relationship between MR response and wear behavior appears to be of fundamental importance. One of the fluids(MR#1)contains only the iron microparticles and base oil; the second and third ones(MR#2 and MR#3) contain an anti-wear additive as well. The fourth one(MR#4)is a well known commercial MRF. Finally, MR#5 is stabilized by dispersing the iron particles in a magnetite ferrofluid. The MR response of the latter fluid is better(higher yield stress and post-yield viscosity)than that of the others. More importantly, it remains(and even improves)after the wear test: the pressure applied in the four-ball apparatus produces a compaction of the magnetite layer around the iron microparticles. Additionally, the friction coefficient is larger, which seems paradoxical in principle, but can be explained by considering the stability of MR#5 in comparison to the other four MRs, which appear to undergo partial phase separation during the test. In fact, electron and optical microscope observations confirm a milder wear effect of MR#5, with almost complete absence of scars from the steel test spheres and homogeneous and shallow grooves on them. Comparatively, MR#2, MR#3 and, particularly, MR#1 produce a much more significant wear.MINECO Ramón y Cajal Programme (RYC-2014-16901)MINECO FIS 2013-07666-C3-1-RCEI Biotic BS27.2015Junta de Andalucía, PE2012-FQM-069

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Rheological properties of magnetic biogels

We report an experimental and theoretical study of the rheological properties of magnetic biogels consisting of fibrin polymer networks with embedded magnetite nanoparticles, swollen by aqueous solutions. We studied two types of magnetic biogels, differenced by the presence or absence of an applied magnetic field during the initial steps of cross-linking. The experiments demonstrated very strong dependence of the elastic modulus of the magnetic biogels on the concentration of the magnetic particles. We finally developed some theoretical models that explain the observed strong concentration effects.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, MINECO, Spain, co-funded by ERDF, European Union) and FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, andAgencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). A.Z. is grateful to the program of the Ministry of Education and Science of the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7, as well as to the Russian Fund of Basic Researches, project 18-08-00178

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Comparación de distintas estrategias para la predicción de muerte a corto plazo en el paciente anciano infectado

Objective. The aim of this study was to determine the utility of a post hoc lactate added to SIRS and qSOFA score to predict 30-day mortality in older non-severely dependent patients attended for infection in the Emergency Department (ED). Methods. We performed an analytical, observational, prospective cohort study including patients of 75 years of age or older, without severe functional dependence, attended for an infectious disease in 69 Spanish ED for 2-day three seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event. Results. We included 739 patients with a mean age of 84.9 (SD 6.0) years; 375 (50.7%) were women. Ninety-one (12.3%) died within 30 days. The AUC was 0.637 (IC 95% 0.587-0.688; p= 2 and 0.698 (IC 95% 0.635- 0.761; p= 2. Comparing receiver operating characteristic (ROC) there was a better accuracy of qSOFA vs SIRS (p=0.041). Both scales improve the prognosis accuracy with lactate inclusion. The AUC was 0.705 (IC95% 0.652-0.758; p<0.001) for SIRS plus lactate and 0.755 (IC95% 0.696-0.814; p<0.001) for qSOFA plus lactate, showing a trend to statistical significance for the second strategy (p=0.0727). Charlson index not added prognosis accuracy to SIRS (p=0.2269) or qSOFA (p=0.2573). Conclusions. Lactate added to SIRS and qSOFA score improve the accuracy of SIRS and qSOFA to predict short-term mortality in older non-severely dependent patients attended for infection. There is not effect in adding Charlson index

Combinatorial entropy behaviour leads to range selective binding in ligand receptor interactions

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent e ects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a speci ed range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs