Utilización de microhilos magnéticos para promover la muerte de células de osteosarcoma mediante hipertermia magnética in vitro

Los tratamientos para el cáncer que se llevan a cabo actualmente tienen una serie de limitaciones que, unido a que se trata de técnicas invasivas, hace que se tienda a buscar nuevas alternativas. Una de ellas es la hipertermia dirigida, cuyo objetivo son las células cancerígenas. Se trata de una técnica relativamente nueva, por lo que aún no se ha estudiado en profundidad. En este trabajo, se han utilizado microhilos magnéticos amorfos recubiertos de vidrio para calentar células de osteosarcoma aplicando un campo magnético alterno. De acuerdo con los resultados obtenidos de los ensayos realizados “in vitro”, se puede confirmar que la utilización de estos microhilos magnéticos reduce la proliferación de células cancerígenas dando lugar finalmente a la muerte celular. Además, esta técnica es un proceso mucho menos invasivo que los utilizados actualmente y que requiere exposiciones breves a campos magnéticos débiles. Por todo esto, la hipertermia dirigida se presenta como una alternativa efectiva para el tratamiento de osteosarcoma.Por último, agradecer a Tamag Ibérica S.L. por proporcionarnos los microhilos magnéticos para poder llevar a cabo este estudio y a Fomento de San Sebastián por financiar el proyecto de investigació

INTEGRAL observations of the Be/X-ray binary EXO 2030+375 during outburst

We present a type-I outburst of the high-mass X-ray binary EXO 2030+375, detected during INTEGRAL's Performance and Verification Phase in December 2002 (on-source time about 10e+06 seconds). In addition, six more outbursts have been observed during INTEGRAL's Galactic Plane Scans. X-ray pulsations have been detected with a pulse period of 41.691798+-0.000016 s. The X-ray luminosity in the 5-300 keV energy range was 9.7*10e+36 erg/s, for a distance of 7.1 kpc. Two unusual features were found in the light curve, with an initial peak before the main outburst and another possible spike after the maximum. RXTE observations confirm only the existence of the initial spike. Although the initial peak appears to be a recurrent feature, the physical mechanisms producing it and the possible second spike are unknown. Moreover, a four-day delay between periastron passage and the peak of the outburst is observed. We present for the first time a 5-300 keV broad-band spectrum of this source. It can be modelled by the sum of a disk black body (kT_bb~8 keV) with either a power law model with Gamma=2.04+-0.11 keV or a Comptonized component (spherical geometry, kT_e=30 keV, tau=2.64, kT_W=1.5 keV).Comment: 10 pages, 11 figures, to be published in A&

Curie temperature enhancement of electron doped Sr2_2FeMoO6_6 perovskites studied by photoemission spectroscopy

We report here on the electronic structure of electron-doped half-metallic ferromagnetic perovskites such Sr$_{2-x}$La$_x$FeMoO$_6$ ($x$=0-0.6) as obtained from high-resolved valence-band photoemission spectroscopy (PES). By comparing the PES spectra with band structure calculations, a distinctive peak at the Fermi level (E$_F$) with predominantly (Fe+Mo) t$_{2g}^\downarrow$ character has been evidenced for all samples, irrespectively of the $x$ values investigated. Moreover, we show that the electron doping due to the La substitution provides selectively delocalized carriers to the t$_{2g}^\downarrow$ metallic spin channel. Consequently, a gradual rising of the density of states at the E$_F$ has been observed as a function of the La doping. By changing the incoming photon energy we have shown that electron doping mainly rises the density of states of Mo parentage. These findings provide fundamental clues for understanding the origin of ferromagnetism in these oxides and shall be of relevance for tailoring oxides having still higher T$_C$

Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150–154 Mb), Oar6 (4–49 Mb) and Oar13 (68–74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.Publishe

Utilización de microhilos magnéticos para promover la muerte de células de osteosarcoma mediante hipertermia magnética in vitro

Los tratamientos para el cáncer que se llevan a cabo actualmente tienen una serie de limitaciones que, unido a que se trata de técnicas invasivas, hace que se tienda a buscar nuevas alternativas. Una de ellas es la hipertermia dirigida, cuyo objetivo son las células cancerígenas. Se trata de una técnica relativamente nueva, por lo que aún no se ha estudiado en profundidad. En este trabajo, se han utilizado microhilos magnéticos amorfos recubiertos de vidrio para calentar células de osteosarcoma aplicando un campo magnético alterno. De acuerdo con los resultados obtenidos de los ensayos realizados “in vitro”, se puede confirmar que la utilización de estos microhilos magnéticos reduce la proliferación de células cancerígenas dando lugar finalmente a la muerte celular. Además, esta técnica es un proceso mucho menos invasivo que los utilizados actualmente y que requiere exposiciones breves a campos magnéticos débiles. Por todo esto, la hipertermia dirigida se presenta como una alternativa efectiva para el tratamiento de osteosarcoma.Por último, agradecer a Tamag Ibérica S.L. por proporcionarnos los microhilos magnéticos para poder llevar a cabo este estudio y a Fomento de San Sebastián por financiar el proyecto de investigació

Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted

GRO J1008-57: an (almost) predictable transient X-ray binary

A study of archival RXTE, Swift, and Suzaku pointed observations of the transient high-mass X-ray binary GRO J1008−57 is presented. A new orbital ephemeris based on pulse arrival-timing shows the times of maximum luminosities during outbursts of GRO J1008−57 to be close to periastron at orbital phase − 0.03. This makes the source one of a few for which outburst dates can be predicted with very high precision. Spectra of the source in 2005, 2007, and 2011 can be well described by a simple power law with high-energy cutoff and an additional black body at lower energies. The photon index of the power law and the black-body flux only depend on the 15–50 keV source flux. No apparent hysteresis effects are seen. These correlations allow us to predict the evolution of the pulsar’s X-ray spectral shape over all outbursts as a function of just one parameter, the source’s flux. If modified by an additional soft component, this prediction even holds during GRO J1008−57’s 2012 type II outburst

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients with Inflammatory Bowel Disease: Results from the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn''s disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial

(R.M. Lamuela-Raventos). + MODEL Please cite this article in press as: Medina-Remón A, et al., Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Abstract Background and aim: Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting onequarter of the world&apos;s adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk. Methods and results: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of À1.9 mm Hg [95% confidence interval (CI): À3.4; À0.6] and À2.6 mm Hg (CI: À4.2; À1.0), respectively, and reduced diastolic BP of À1.5 mm Hg (CI: À2.3; À0.6) and À1.9 mm Hg (CI: À2.8; À1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR Z 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR Z 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group. Conclusions: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe.