Cell bystander effect induced by radiofrequency electromagnetic fields and magnetic nanoparticles

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy.Comment: 16 pages, 4 figures, submitted to International Journal of Radiation Biolog

Multi-Scale Modelling of Aggregation of TiO2 Nanoparticle Suspensions in Water

Titanium dioxide nanoparticles have risen concerns about their possible toxicity and the European Food Safety Authority recently banned the use of TiO2 nano-additive in food products. Following the intent of relating nanomaterials atomic structure with their toxicity without having to conduct large-scale experiments on living organisms, we investigate the aggregation of titanium dioxide nanoparticles using a multi-scale technique: starting from ab initio Density Functional Theory to get an accurate determination of the energetics and electronic structure, we switch to classical Molecular Dynamics simulations to calculate the Potential of Mean Force for the connection of two identical nanoparticles in water; the fitting of the latter by a set of mathematical equations is the key for the upscale. Lastly, we perform Brownian Dynamics simulations where each nanoparticle is a spherical bead. This coarsening strategy allows studying the aggregation of a few thousand nanoparticles. Applying this novel procedure, we find three new molecular descriptors, namely, the aggregation free energy and two numerical parameters used to correct the observed deviation from the aggregation kinetics described by the Smoluchowski theory. Ultimately, molecular descriptors can be fed into QSAR models to predict the toxicity of a material knowing its physicochemical properties, enabling safe design strategies

Magnetic hyperthermia enhances cell toxicity with respect to exogenous heating

Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures. Human neuroblastoma SH-SY5Y cells were loaded with magnetic nanoparticles (MNPs) and packed into dense pellets to generate an environment that is crudely similar to that expected in solid micro-tumors, and the above-mentioned protocols were applied to these cells. These experiments showed that for the same target temperatures, MHT induces a decrease in cell viability that is larger than the corresponding EHT, up to a maximum difference of approximately 45% at T = 46 °C. An analysis of the data in terms of temperature efficiency demonstrated that MHT requires an average temperature that is 6 °C lower than that required with EHT to produce a similar cytotoxic effect. An analysis of electron microscopy images of the cells after the EHT and MHT treatments indicated that the enhanced effectiveness observed with MHT is associated with local cell destruction triggered by the magnetic nano-heaters. The present study is an essential step toward the development of innovative adjuvant anti-cancer therapies based on local hyperthermia treatments using magnetic particles as nano-heaters

Cognitive and functional differences in aging with and without intellectual disabilities: Observational study

The lifespan of people with cognitive disabilities (ID) has increased significantly, but the cognitive aspects together with the functional ones comparing normal aging and those with intellectual disabilities had not been previously studied. Objective: This study analyzed the cognitive and functional differences in older adults aging with ID (and with DS), compared with their peers without disabilities, in order to identify the most adapted interventions. Methodology: This study evaluated the outcome variables of MEC, Set-Test, Barthel, Lawton–Brody, and Tinetti with 247 participants: 146 without ID and 101 ID (29 with DS and 72 without DS). Results: At the cognitive level, older people with ID presented lower scores both in MEC (p < 0.01), globally and in each cognitive domain (except in short-term memory), and in verbal fluency (Set-Test) than older people without ID; however, the diagnosis of cognitive impairment and dementia is higher in people without ID. At the functional level, there are no differences in ABDL, but there are in AIDL and Tinetti (p < 0.01), where participants without ID obtain higher scores. The most frequent pathologies in people with ID were obesity and epilepsy. Conclusions: The lower cognitive and functional performance in ID is associated with the disability itself, the low educational level, the neurocognitive underdiagnosis, and the use of poorly adapted assessment tools. The cognitive and functional results indicated the importance of interventions adapted to the characteristics of this population, in their aging process. © 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Movement representation strategies as a tool for educational innovation in physiotherapy students: a randomized single-blind controlled-pilot trial

Physiotherapy has a strictly theoretical body of knowledge, but for the most part, the physiotherapist’s learning is practical. The practical part is fundamental to acquire clinical skills that the physiotherapist will later use in professional practice. The main aim of this study was to assess the effectiveness of movement representation strategies (MRS) in the improvement of manual skills of physiotherapy students as an educational innovation strategy. We randomly assigned 30 participants to an action observation practice (AOP), motor imagery practice (MIP), or sham observation (SO) group. A high velocity, low amplitude lumbar manipulation technique that is widely used in clinical physiotherapy practice was taught in one session. The primary outcomes were required time and test score. The secondary outcomes were perceived mental fatigue and perceived difficulty for learning. The outcomes were assessed preintervention and immediately after the intervention (postintervention). The main results showed that both AOP and MIP improved the total time required and the test score, as well as entailed less perceived difficulty for learning. However, both strategies showed a higher level of mental fatigue after the intervention, which was higher in the MIP group. Based on the results obtained, it seems that the application of MRS promotes greater learning of manual motor tasks in physiotherapy students and could be used as educational innovation strategies

Self-assembly, binding ability and magnetic properties of dicopper(ii) pyrazolenophanes

A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu-2(mu-4-Mepz)(2)(mu-ClO4)(ClO4)(bpm)(2)] (1), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(4,7-Me(2)phen)(2)]ClO4 center dot H2O center dot CH3CN (2), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(3/2)(H2O)(1/2)(phen)(2)](2)[Cu-2(mu-pz)(2)(mu-ClO4)(ClO4)(2)(phen)(2)]center dot 8H(2)O (3), and [Cu-2(mu-pz)(2)(CH3CN)(2)(3,4,7,8-Me(4)phen)(2)](ClO4)(2) (4) (Hpz = pyrazole, H-4-Mepz = 4-methylpyrazole, bpm = 2,2'-bipyrimidine, phen = 1,10-phenanthroline, 4,7-Me(2)phen = 4,7-dimethyl-1,10-phenanthroline, and 3,4,7,8-Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) have been synthesized and magneto-structurally investigated. The crystal structures of 1-4 contain bis(pyrazolate)(perchlorate)-(1 and 3), bis(pyrazolate)(aqua)-(2 and 3), or bis(pyrazolate)-bridged (4) dicopper(II) entities of the metallacyclophane-type with bpm (1), 4,7-Me(2)phen (2), phen (3), and 3,4,7,8-Me(4)phen (4) as blocking bidentate ligands. All of them exhibit a saddle conformation with an overall not planar but bent, six-membered Cu-(N-N')(2)-Cu metallacyclic core with relatively short intermetallic distances across the bis(pyrazolate)(perchlorate) [r = 3.3076(5) (1) and 3.382(1) angstrom (3)], bis(pyrazolate)(aqua) [r = 3.383(1) (2) and 3.357(1) angstrom (3)], and bis(pyrazolate) bridges [r = 3.098(1) angstrom (4)]. The analyses of the variable-temperature magnetic susceptibility of 1-4 reveal the occurrence of a moderately strong antiferromagnetic coupling across the bis(pyrazolate)(perchlorate) [-J = 228 (1) and 193 cm(-1) (3)], bis(pyrazolate)(aqua) [-J = 189 (2) and 221 cm(-1) (3)], and bis(pyrazolate) bridges [-J = 197 cm(-1) (4)] (the spin Hamiltonian being defined as H = -JS(1).S-2 with S-1 = S-2 = S-Cu = 1/2).A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu2(μ-4-Mepz)2(μ-ClO4)(ClO4)(bpm)2] (1), [Cu2(μ-pz)2(μ-H2O)(ClO4)(4,7-Me2phen)2]ClO4·H2O·CH3CN (2), [Cu2(μ-pz)2(μ-H2O)(ClO4)3/2(H2O)1/2(phen)2]2[Cu2(μ-pz)2(μ-ClO4)(ClO4)2(phen)2]·8H2O183437449COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESsem informaçãoThis work was supported by the Ministerio Español de Economía y Competitividad (Project CTQ2013-44844P and Unidad de Excelencia MDM-2015-0538) and the Generalitat Valenciana (PROMETEOII/2014/070). We also acknowledge the financial support from Brazilian