Gold nanoparticles crossing blood-brain barrier prevent HSV-1 infection and reduce herpes associated amyloid-βsecretion

Infections caused by HSV-1 and their typical outbreaks invading the nervous system have been related to neurodegenerative diseases. HSV-1 infection may deregulate the balance between the amyloidogenic and non-amyloidogenic pathways, raising the accumulation of amyloid-β peptides, one of the hallmarks in the neurodegenerative diseases. An effective treatment against both, HSV-1 infections and neurodegeneration, is a major therapeutic target. Therefore, gold nanoparticles (NPAus) have been previously studied in immunotherapy, cancer and cellular disruptions with very promising results. Our study demonstrates that a new NPAus family inhibits the HSV-1 infection in a neural-derived SK-N-MC cell line model and that this new NPAus reduces the HSV-1-induced β-secretase activity, as well as amyloid-β accumulation in SK-APP-D1 modifies cell line. We demonstrated that NPAuG3-S8 crosses the blood-brain barrier (BBB) and does not generate cerebral damage to in vivo CD1 mice model. The NPAuG3-S8 could be a promising treatment against neuronal HSV-1 infections and neuronal disorders related to the Aβ peptidesThis work has been (partially) funded by the RD16/0025/0019, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013-2016) and cofinanced by Instituto de Salud Carlos III (Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant numbers: PI16/01863; PI19/01638) and EPIICAL project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology

Prevalencia de hipotensión ortostática en ancianos hipertensos tratados en atención primaria

ObjetivoConocer la prevalencia de hipotensión ortostática (HO) y los factores asociados en ancianos hipertensos tratados en atención primaria (AP).DiseñoEstudio descriptivo, transversal.EmplazamientoCentro de Salud La Marina (centro urbano en Santander).PacientesUna muestra aleatoria de 295 pacientes de 65 o más años atendidos regularmente por presentar hipertensión arterial (HTA).Mediciones y resultados principalesSe han obtenido cifras de presión arterial (PA) en sedestación y en bipedestación. La definición de HO utilizada ha sido: disminución de 20 mmHg o más en la PA sistólica (PAS) o de 10 mmHg o más en la PA diastólica (PAD), tras 1 o 5 minutos de bipedestación. También se han recogido datos sobre enfermedades asociadas, síntomas en bipedestación, medicación utilizada, hábitos de los pacientes y resultados de otras exploraciones clínicas. La prevalencia global encontrada de HO fue del 14,6%. La prevalencia de HO sistólica tras un minuto (HO-S1) y tras 5 minutos (HO-S5) de bipedestación ha sido del 5,8% en ambas, y la de HO diastólica del 5,1% tras un minuto (HO-D1) y del 4,1% tras 5 minutos (HO-D5) de bipedestación. En el análisis de regresión logística se encontró una asociación entre la existencia de HO global y la mayor elevación de la PA sistólica inicial, la presencia de síntomas de intolerancia ortostática (aunque sólo un 25,6% de los pacientes con HO presentaba síntomas) y el hábito tabáquico. Asimismo, se encontró una asociación con el uso de bloqueadores beta y antagonistas del calcio (diferentes de las dihidropiridinas) y la existencia de HO al minuto de bipedestación, y entre el consumo de tabaco y la HO a los 5 minutos de bipedestación.ConclusionesLa prevalencia detectada es alta y justifica la búsqueda sistemática de HO en los pacientes ancianos que son tratados de HTA en AP. La existencia de síntomas con el ortostatismo se relaciona con una mayor prevalencia de HO, pero sólo los presentó uno de cada 4 pacientes con HO. El consumo de tabaco podría estar relacionado con la presencia de HO, así como el uso de bloqueadores beta y antagonistas del calcio (diferentes de las dihidropiridinas).ObjectiveTo find the prevalence of orthostatic hypotension (OH) and associated factors in elderly hypertensive patients in a primary care setting.DesignDescriptive cross-sectional study.SettingLa Marina Health Centre (an urban centre in Santander).PatientsA random sample of 295 patients aged 65 years or older regularly assisted from hypertension.Measurements and main resultsMeasurements of sitting and standing blood pressure were obtained. Orthostatic hypotension was defined as 20 mmHg or greater decrease in systolic or 10 mmHg or greater decrease in diastolic blood pressure after 1-minute or 5-minute standing. Associated diseases, symptoms upon standing, medication use, habits and other clinical assessments were also recorded. The prevalence of OH was 14.6%. The prevalence of systolic OH after 1-minute (OH-S1) and after 5-minute (OH-S5) standing was 5.8% in both, and the diastolic OH was 5.1% after 1-minute (OH-D1) and 4.1% after 5-minute (OH-D5) standing. By logistic regression analysis, association between higher level of systolic blood pressure and global OH was found, also with the presence of orthostatic intolerance symptoms (although only 25.6% of the patients with OH showed symptoms) and smoking. Beta-blockers and calcium channel blockers (different from dihydropyridines) use was associated with OH after 1-minute standing and smoking with OH after 5-minute standing.ConclusionsThe detected prevalence is high and justifies the case finding of OH in elderly hypertensive patients in primary care. The symptoms of orthostatic intolerance are correlated with OH, but only 1 out of 4 patients showed symptoms. Smoking could be related with OH, so beta-blockers and calcium channel blockers (different from dihydropyridines) use

Gravity, p-branes and a spacetime counterpart of the Higgs effect

We point out that the worldvolume coordinate functions $\hat{x}^\mu(\xi)$ of a $p$-brane, treated as an independent object interacting with dynamical gravity, are Goldstone fields for spacetime diffeomorphisms gauge symmetry. The presence of this gauge invariance is exhibited by its associated Noether identity, which expresses that the source equations follow from the gravitational equations. We discuss the spacetime counterpart of the Higgs effect and show that a $p$-brane does not carry any local degrees of freedom, extending early known general relativity features. Our considerations are also relevant for brane world scenarios.Comment: 5 pages, RevTeX. v2 (30-IV-03) with additional text and reference

Supergravity interacting with bosonic p-branes and local supersymmetry

We study the coupling of supergravity with a purely bosonic brane source (bosonic p-brane). The interaction, described by the sum of their respective actions, is self-consistent if the bosonic p-brane is the pure bosonic limit of a super-p-brane. In that case the dynamical system preserves 1/2 of the local supersymmetry characteristic of the `free' supergravity.Comment: 11 pages, RevTe

On BPS preons, generalized holonomies and D=11 supergravities

We develop the BPS preon conjecture to analyze the supersymmetric solutions of D=11 supergravity. By relating the notions of Killing spinors and BPS preons, we develop a moving G-frame method (G=GL(32,R), SL(32,R) or Sp(32,R)) to analyze their associated generalized holonomies. As a first application we derive here the equations determining the generalized holonomies of k/32 supersymmetric solutions and, in particular, those solving the necessary conditions for the existence of BPS preonic (31/32) solutions of the standard D=11 supergravity. We also show that there exist elementary preonic solutions, i.e. solutions preserving 31 out of 32 supersymmetries in a Chern--Simons type supergravity. We present as well a family of worldvolume actions describing the motion of pointlike and extended BPS preons in the background of a D'Auria-Fre type OSp(1|32)-related supergravity model. We discuss the possible implications for M-theory.Comment: 11 pages, RevTeX Typos corrected, a short note and references adde

Supersymmetry and Integrability in Planar Mechanical Systems

We present an N=2-supersymmetric mechanical system whose bosonic sector, with two degrees of freedom, stems from the reduction of an SU(2) Yang-Mills theory with the assumption of spatially homogeneous field configurations and a particular ansatz imposed on the gauge potentials in the dimensional reduction procedure. The Painleve test is adopted to discuss integrability and we focus on the role of supersymmetry and parity invariance in two space dimensions for the attainment of integrable or chaotic models. Our conclusion is that the relationships among the parameters imposed by supersymmetry seem to drastically reduce the number of possibilities for integrable interaction potentials of the mechanical system under consideration.Comment: 20 pages, 3 figure

Application of a dynamic event tree methodolgy to steam generator tube rupture sequences

The Integrated Safety Assessment (ISA) methodology, developed by the Spanish Nuclear Safety Council (CSN), has been applied to a thermo-hydraulical analysis of a Westinghouse 3-loop PWR plant by means of the dynamic event trees (DET) for Steam Generator Tube Rupture (SGTR) sequences. The ISA methodology allows obtaining the SGTR Dynamic Event Tree taking into account the operator actuation times. Simulations are performed with SCAIS (Simulation Code system for Integrated Safety Assessment), which includes a dynamic coupling with MAAP thermal hydraulic code. The results show the capability of the ISA methodology and SCAIS platform to obtain the DET of complex sequences

Inteligencia Artificial en Medicina y Salud: revisión y clasificación de las aplicaciones actuales y del futuro cercano y su impacto ético y social

This paper provides an overview of the current and near-future applications of Artificial Intelligence (AI) in Medicine and Health Care and presents a classification according to their ethical and societal aspects, potential benefits and pitfalls, and issues that can be considered controversial and are not deeply discussed in the literature. This work is based on an analysis of the state of the art of research and technology, including existing software, personal monitoring devices, genetic tests and editing tools, personalized digital models, online platforms, augmented reality devices, and surgical and companion robotics. Motivated by our review, we present and describe the notion of “extended personalized medicine”, we then review existing applications of AI in medicine and healthcare and explore the public perception of medical AI systems, and how they show, simultaneously, extraordinary opportunities and drawbacks that even question fundamental medical concepts. Many of these topics coincide with urgent priorities recently defined by the World Health Organization for the coming decade. In addition, we study the transformations of the roles of doctors and patients in an age of ubiquitous information, identify the risk of a division of Medicine into “fake-based”, “patient-generated”, and “scientifically tailored”, and draw the attention of some aspects that need further thorough analysis and public debate

Putting string/string duality to the test

After simultaneous compactification of spacetime and worldvolume on $K3$, the $D=10$ heterotic fivebrane with gauge group $SO(32)$ behaves like a $D=6$ heterotic string with gauge group $SO(28) \times SU(2)$, but with Kac--Moody levels different from those of the fundamental string. Thus the string/fivebrane duality conjecture in $D=10$ gets replaced by a string/string duality conjecture in $D=6$. Since $D=6$ strings are better understood than $D=10$ fivebranes, this provides a more reliable laboratory in which to test the conjecture. According to string/string duality, the Green--Schwarz factorization of the $D=6$ spacetime anomaly polynomial $I_{8}$ into $X_4\, \tilde{X}_4$ means that just as $X_4$ is the $\sigma$-model anomaly polynomial of the fundamental string worldsheet so $\tilde{X}_4$ should be the corresponding polynomial of the dual string worldsheet. To test this idea we perform a classical dual string calculation of $\tilde{X}_4$ and find agreement with the quantum fundamental string result. This also provides an {\it a posteriori} justification for assumptions made in a previous paper on string/fivebrane duality. Finally we speculate on the relevance of string/string duality to the vacuum degeneracy problem.Comment: Replaced by version to appear in Nucl. Phys.

Kinetics of 99Tc speciation in aerobic soils

© 2019 The Authors Technetium-99 is a significant and long-lived component of spent nuclear fuel relevant to long-term assessments of radioactive waste disposal. Whilst 99Tc behaviour in poorly aerated environments is well known, the long-term bioavailability in aerobic soils following direct deposition or transport to the surface is less well understood. This work addresses two questions: (i) to what extent do soil properties control 99Tc kinetics in aerobic soils and (ii) over what experimental timescales must 99Tc kinetics be measured to make reliable long-term predictions of impact in the terrestrial environment? Soil microcosms spiked with 99TcO4− were incubated for 2.5 years and 99Tc transformations were periodically monitored by a sequential extraction, which enabled quantification of the reaction kinetics. Reduction in soluble 99Tc was slow and followed a double exponential kinetic model including a fast component enhanced by low pH, a slow component controlled by pH and organic matter, and a persistently soluble 99Tc fraction. Complexation with soil humus was key to the progressive immobilisation of 99Tc. Evidence for slow transfer to an unidentified ‘sink’ was found, with estimated decadal timeframes. Our data suggest that short-term experiments may not reliably predict long-term 99Tc solubility in soils with low to moderate organic matter contents