Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2+) or negative (COOH-) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.Comment: In Press. 33 pages, 11 figure

La virtualización de la economía. La compra de comida por Internet : el consumo, el dinero y el trabajo como acontecimiento

Partiendo de un concepto de virtualización de la economía, donde las prácticas económicas se definen como procesos de desterritorialización y asumiendo que las TICs posibilitan nuevas formas de socialidad, en el presente trabajo se explora una práctica que nos habla de la economía como acontecimieto: La adquisición de comida, a través de Internet. La compra de comida es una práctica singularmente afectiva, que ha expresado a lo largo de la historia diversas formas de socialidad (la compra en el mercado tradicional difiere de la compra en el supermercado). En el presente trabajo exploramos una nueva forma de compra de alimentos, la compra por Internet y analizamos en ella el acontecer económico a partir de tres ejes: el consumo, el dinero y el trabajo.Starting from an economy virtualization concept, where economic practices are defined as de-territorialization processes, and assuming that ICTs (information and communication technologies) make possible new ways for sociality, this paper explores a practice that draws economy as a happening. The acquisition of food through the Internet. Food purchasing is a singularily affective practice, which through history has shown different forms of sociality (traditional market purchasing differs from supermarket purchasing). In this paper we explore a new way of buying food, Internet purchasing, analizing in it the economic happening through three axis: consumption, money and work

Forearm Muscle Activity During the Handgrip Test in Breast Cancer Survivors: A Cross-Sectional Study

We recruited 102 breast cancer survivors at a secondary care in Malaga. Included breast cancer survivors showed a good upper limb functionality but a reduced forearm muscle activity. Forearm muscle activity showed a poor significant correlation with the cancer-related fatigue . Handgrip strength also showed a poor correlation with the upper limb functionality. Both outcomes tended to lower values with higher levels of cancer-related fatigue. Introduction/Background: Breast cancer survivors (BCS) frequently show upper limb dysfunctions. The forearm muscle activity measured by surface electromyography (sEMG) in this population has not been studied. This study aimed to describe forearm muscle activity in BCS, as well as to assess its possible relationship with other variables related to upper limb functionality and cancer-related fatigue (CRF). Materials and Methods: A cross-sectional study was carried out including 102 BCS as volunteers at a secondary care in Malaga, Spain. BCS were included if they were aged between 32 and 70 years old, without evidence of cancer recurrence at the time of recruitment. The forearm muscle activity (microvolts, μV) was assessed by sEMG during the handgrip test. The handgrip strength was assessed by dynamometry (kg), the upper limb functionality (%) was measured by the upper limb functional index (ULFI) question- naire and the CRF was also assessed by revised Piper Fatigue Scale (0-10 points). Results: BCS reported reduced forearm muscle activity (287.88 μV) and reduced handgrip strength (21.31 Kg), a good upper limb functionality (68.85%), and a moderate cancer-related fatigue (4.74). Forearm muscle activity showed a poor significant correlation (r = –0.223, P = .038) with the CRF. Handgrip strength showed a poor correlation with the upper limb functionality (r = 0.387, P < .001) and age (r=-0.200, P = .047)...Funding for open access charge: Universidad de Málaga /CBU

Latest Cretaceous palaeogeographic evolution of northeast Iberia: Insights from the Campanian continental Montalbán subbasin (Spain)

This work characterizes for the first time the 500–700 m-thick uppermost Cretaceous continental sedimentary succession of the Allueva Fm recorded in the northeastern margin of the Iberian basin, in the Montalbán subbasin (Maestrazgo domain, Spain). The middle-upper Campanian age of this unit constrained here by new paleomagnetic and biostratigraphic data involves major revision of previous stratigraphic and palaeogeographic interpretations. The uplift of the northern marginal areas of the Montalbán subbasin onwards from the middle Campanian supplied the coarse terrigenous-clastic sediments common in the alluvial Allueva Fm. Moreover, a sharp increase of the sedimentation rates (from 4 to 19 cm/ky) from the lower to the middle-upper part of the Allueva Fm has been related to further increase of the tectonic activity during the middle part of the late Campanian. Also relevant are the new discovered vertebrate sites mostly found in the marginal areas of a large lacustrine-palustrine carbonate system developed during the latest Campanian. Vertebrate sites include a fossil assemblage with abundance of titanosaur sauropod dinosaurs as well as the presence of ornithopod dinosaurs and crocodylomorphs. A review of the dinosaur fossil sites recorded in other Iberian subbasins shows a similar fossil assembage occurrence during the late Campanian–earliest Maastrichtian timespan, previous to the faunal turnover that took place in the Ibero-Armorican landmass around the onset of the late Maastrichtian. The stratigraphic, sedimentological and paleontological characterization of the successions recorded during the initial stages of development of the Montalbán subbasin have major implication to understand the latest Cretaceous palaeogeographic evolution of northeast Iberia. Comparative review to other latest Cretaceous continental successions deposited in other domains of the Iberian basin indicates a south to north migration of newly developed subsident subbasins: during the Campanian (South Iberian domain), during the middle-late Campanian (northern Maestrazgo domain), and during the Maastrichtian (central Castillian domain)

Desplazamiento de conidias de Metarhizium anisopliae var. anisopliae en columnas de tres series de suelo

The fungus Metarhizium anisopliae isolationQu-M270 is a promising control agent for the wheat white grub( Hylamorpha elegans Burm.), a Chilean scarabeid species whose larvae feed on roots of diverse crops and move in soil up to a depth of 25 cm. In this study, the vertical movement of Qu- M270 conidias suspended in water was evaluated in three soil series from the B\uedo-B\uedo Region (36\ub032' S lat; 71\ub055' W long), Chile. Soil was obtained using PVC pipes 30 cm long by 20 cm in diameter. Conidia recovery was performed in a specific medium for Metarhizium anisopliae, by counting colony forming units in 1 g of dry soil. The Quella series (Aquic Durixerets) was more restrictive to the percolation of conidia, which were concentrated at the first 10 cm. With the Arenales series (Dystric Xeropsamments), conidia were found below 15 cm and in percolated liquids. On the other hand, the Mirador series (Ultic Palexeralf) had a uniform distribution of conidia at every depth.El hongo entomopat\uf3geno Metarhizium anisopliae , aislamiento Qu-M270, es espec\uedfico para el control del gusano blanco del trigo ( Hylamorpha elegans Burm.), el cual se alimenta de ra\uedces de diversos cultivos y se desplaza en el perfil del suelo hasta los 25 cm de profundidad. En este estudio se evalu\uf3 el desplazamiento vertical de conidias de Qu-M270, en suspensi\uf3n acuosa, a trav\ue9s de columnas de suelo extra\ueddas con tubos de PVC de 30 cm de largo y 20 cm de di\ue1metro, en tres series de suelo de la Regi\uf3n del B\uedo-B\uedo (36\ub032' lat. Sur; 71\ub055' long. Oeste), Chile. La recuperaci\uf3n de conidias se realiz\uf3 en medio especifico para Metarhizium anisopliae, contabilizando unidades formadoras de colonias por gramo de suelo seco. La serie Quella (Aquic Durixerets) fue m\ue1s restrictiva al paso de conidias, las que se concentraron en los primeros 10 cm de profundidad, a diferencia de la serie Arenales (Dystric Xeropsamments) en que se observ\uf3 su presencia bajo los 15 cm y en los l\uedquidos percolados. La serie Mirador (Ultic Palexeralf) present\uf3 una distribuci\uf3n uniforme a lo largo de todo el perfil

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by Bradykinin. Part. II: treatment, follow-up, and special situations

Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientifi c evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientifi c papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor defi ciency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus. Results: Treatment approaches are discussed, and the consensus reached is described. Specifi c situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation. Conclusions: A review of and consensus on treatment of bradykinin-induced angioedema is presentedIntroducción: No existen guías previas españolas sobre el manejo del angioedema mediado por bradicinina. Objetivos: Alcanzar un consenso sobre el manejo y tratamiento del angioedema mediado por bradicinina a la luz de la evidencia científi ca disponible y la experiencia de los expertos, que sirva como guía para los profesionales de la salud. Métodos: SGBA/GEAB, un grupo de trabajo de la SEAIC dirigió el consenso. Se realizó una revisión de los documentos científi cos publicados sobre los diferentes tipos de angioedema mediado por bradicinina [angioedema hereditario o adquirido por defi ciencia de inhibidor de la C1 esterasa, angioedema hereditario relacionado con estrógenos (AEH tipo III, AEH-FXII), angioedema inducido por IECA (inhibidores del enzima convertidor de angiotensina]. Hubo varias reuniones del SGBA/GEAB para alcanzar el consenso. Resultados: Se revisan y discuten los diferentes tratamientos disponibles y se describe el consenso alcanzado. Se abordan situaciones específi cas (embarazo, anticoncepción, viajes, hemodonación, trasplante de órganos). Conclusiones: Se presenta una revisión del tratamiento del angioedema mediado por bradicinina y un consenso sobre su tratamiento en EspañaDr. Teresa Caballero is a researcher with the Hospital La Paz Health Research Institute (IdiPaz) program for promoting research activities (2009

Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families

Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients

Fanconi anemia (FA) is caused by biallelic mutations in FA genes. Monoallelic mutations in five of these genes (BRCA1, BRCA2, PALB2, BRIP1 and RAD51C) increase the susceptibility to breast/ovarian cancer and are used in clinical diagnostics as bona-fide hereditary cancer genes. Increasing evidence suggests that monoallelic mutations in other FA genes could predispose to tumor development, especially breast cancer. The objective of this study is to assess the mutational spectrum of 14 additional FA genes (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCP, FANCQ, FANCR and FANCU) in a cohort of hereditary cancer patients, to compare with local cancer-free controls as well as GnomAD. A total of 1021 hereditary cancer patients and 194 controls were analyzed using our next generation custom sequencing panel. We identified 35 pathogenic variants in eight genes. A significant association with the risk of breast cancer/breast and ovarian cancer was found for carriers of FANCA mutations (odds ratio (OR) = 3.14 95% confidence interval (CI) 1.4-6.17, p = 0.003). Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk

Spatial and temporal variation in reproduction of a generalist crocodilian, Caiman crocodilus yacare, in a seasonally flooded wetland

We monitored the number of caiman (Caiman crocodilus yacare) nests in two ranches in the Brazilian Pantanal that cover an area of about 50.000 ha for 28 years (1987-2014). The number of nests was related to combinations of rainfall, water level, and number of days with temperature below 20°C, depending on the area. Most of the variation in number of nests could not be predicted by the environmental variables, but could be represented mathematically by a sine wave. We were not able to identify any external driver and suspect that the regular fluctuations may have resulted from an intrinsic population process. Presently, ranches are used as management units under the legislation for ranching Pantanal caimans. However, although some breeding females were recaptured in the area after periods of up to 21 years, most were not recaptured near nests or in general surveys of the area, suggesting that females are not strongly philopatric and that ranches do not represent isolated demographic units. Copyright: © 2015 Campos et al

S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo

BACKGROUND: Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied. RESULTS: S-allylmercaptocysteine was able to scavenge hydroxyl radicals and singlet oxygen in vitro. In rats treated with gentamicin (70 mg/Kg body weight, subcutaneously, every 12 h, for 4 days), renal oxidative stress was made evident by the increase in protein carbonyl content and 4-hydroxy-2-nonenal, and the nitrosative stress was made evident by the increase in 3-nitrotyrosine. In addition, gentamicin-induced nephrotoxicity was evident by the: (1) decrease in creatinine clearance and in activity of circulating glutathione peroxidase, and (2) increase in urinary excretion of N-acetyl-β-D-glucosaminidase, and (3) necrosis of proximal tubular cells. Gentamicin-induced oxidative and nitrosative stress and nephrotoxicity were attenuated by S-allylmercaptocysteine treatment (100 mg/Kg body weight, intragastrically, 24 h before the first dose of gentamicin and 50 mg/Kg body weight, intragastrically, every 12 h, for 4 days along gentamicin-treatment). CONCLUSION: In conclusion, S-allylmercaptocysteine is able to scavenge hydroxyl radicals and singlet oxygen in vitro and to ameliorate the gentamicin-induced nephrotoxicity and oxidative and nitrosative stress in vivo