The effect of age on the acquisition and selection of cancer driver mutations in sun-exposed normal skin.

BACKGROUND: The accumulation of somatic mutations contributes to ageing and cancer. Sunlight is the principal aetiological factor associated with skin cancer development. However, genetic and phenotypic factors also contribute to skin cancer risk. This study aimed at exploring the role of photoaging, as well as other well-known epidemiological risk factors, in the accumulation of somatic mutations in cancer-free human epidermis. MATERIAL AND METHODS: We deeply sequenced 46 genes in normal skin biopsies from 123 healthy donors, from which phenotypic data (including age, pigmentation-related genotype and phenotype) and sun exposure habits were collected. We determined the somatic mutational burden, mutational signatures, clonal selection and frequency of driver mutations in all samples. RESULTS: Our results reveal an exponential accumulation of UV-related somatic mutations with age, matching skin cancer incidence. The increase of mutational burden is in turn modified by an individual's skin phototype. Somatic mutations preferentially accumulated in cutaneous squamous cell carcinoma cancer genes and clonally expanded with age, with distinct mutational processes underpinning different age groups. Our results suggest a loss of fidelity in transcription-coupled repair later in life. CONCLUSION: Our findings reveal that ageing is not only associated with an exponential increase in the number of somatic mutations accumulated in normal epidermis, but also with selection and expansion of cancer-associated mutations. Aged, sun-exposed normal skin is thus an extended mosaic of multiple clones with driver mutations, poised for the acquisition of transforming events.

Immediate and 24-h post-marathon cardiac troponin T is associated with relative exercise intensity.

PURPOSE: We aimed at exploring whether cardiopulmonary fitness, echocardiographic measures and relative exercise intensity were associated with high-sensitivity cardiac troponin T (hs-TNT) rise and normalization following a marathon. METHODS: Nighty-eight participants (83 men, 15 women; 38.72 ± 3.63 years) were subjected to echocardiographic assessment and a cardiopulmonary exercise test (CPET) before the race. hs-TNT was measured before, immediately after and at 24, 48, 96, 144 and 192 h post-race. Speed and mean heart rate (HR) during the race were relativized to CPET values: peak speed (%VVMAX), peak HR (HR%MAX), speed and HR at the second ventilatory threshold (HR%VT2 and %VVT2). RESULTS: Hs-TNT increased from pre- to post-race (5.74 ± 5.29 vs. 50.4 ± 57.04 ng/L; p < 0.001), seeing values above the Upper Reference Limit (URL) in 95% of the participants. At 24 h post-race, 39% of the runners still exceeded the URL (High hs-TNT group). hs-TNT rise was correlated with marathon speed %VVT2 (r = 0.22; p = 0.042), mean HR%VT2 (r = 0.30; p = 0.007), and mean HR%MAX (r = 0.32; p = 0.004). Moreover, the High hs-TNT group performed the marathon at a higher Speed %VVT2 (88.21 ± 6.53 vs. 83.49 ± 6.54%; p = 0.002) and Speed %VVMAX (72 ± 4.25 vs. 69.40 ± 5.53%; p = 0.009). hs-TNT showed no significant associations with cardiopulmonary fitness and echocardiographic measures, except for a slight correlation with left ventricular end systolic diameter (r = 0.26; p = 0.018). CONCLUSION: Post-race hs-TNT was above the URL in barely all runners. Magnitude of hs-TNT rise was correlated with exercise mean HR; whereas, its normalization kept relationship with marathon relative speed.

CoCrPt/Ti perpendicular media onto nanostructured polymer templates.

The fabrication and the study of the magnetic properties of CoCrPt/Ti nanostructures produced by sputtering onto ordered polymer templates are reported here. Samples exhibit a significant out-of-plane component of the magnetization higher than for planar films, and it is stronger for the thicker CoCrPt films, and for nanostructured films with the shorter period ordering. The shape of the polymeric templates plays an important role for the determination of magnetic easy-axis. Magnetic Force Microscopy images of the samples show a single magnetic domain structure with high out-of-plane anisotropy for the samples with longer ordering (480 nm period).

Template-assisted CoPd nanowire arrays: magnetic properties and FORC analysis.

Highly hexagonally ordered CoPd alloy nanowire arrays were synthesized through electrochemical deposition techniques into the nanopores of anodic alumina membranes used as templates. Two different electrolytes were used for this purpose, one with pH = 4.1 and the other with pH = 7. Under applying different electrodeposition parameters and by adjusting both, the current density and the electrolyte composition, it could be possible make to vary the composition of CoPd alloy nanowires in a wide range. Their composition and morphology were investigated by SEM and EDX. The magnetic properties of the nanowires array have been measured with a VSM as a function of the temperature, ranging from RT down to 50 K, for different CoPd alloy nanowires composition. Also, the temperature influence on the reversible-irreversible magnetization processes related with the magnetization reversal of the CoPd nanowires array has been analyzed by first order reversal curve (FORC) method.

Magnetic properties of (Fe, Co)-Pd nanowire arrays.

Ordered arrays of ferromagnetic nanowires with (Fe, Co)-Pd compositions have been fabricated from chloride based electrochemical baths by means of template-assisted electrodeposition into self-assembled nanopores of anodic alumina membranes. The nanowires have a diameter and inter-spacing distance of 72 nm and 105 nm, respectively, and around 0.6-1.6 microm in length. Their microstructure and basic magnetic properties are reported. Coercivity, remanence and respective angular dependences on the applied field up to +/- 3 T have been determined from room temperature hysteresis loops measured in a VSM. The study has been performed paying particular attention to the influence of increasing from about 27 up to 63 percent the Pd content in the nanowire alloy.

Anaesthetic-surgical guide in the treatment of ascending aorta and surgery of the ascending aorta and aortic arch. Consensus document of the Spanish Society of Cardiovascular and Endovascular Surgery and the Sociedad of Anaesthesiology, Resuscitation and Pain Therapy.

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

The week after running a marathon: Effects of running vs elliptical training vs resting on neuromuscular performance and muscle damage recovery.

Our aim was to compare the effects of two exercise modalities vs resting on the time course of neuromuscular performance and muscle damage recovery during the week after running a marathon. Sixty-four finishers from a road marathon completed the study (54 men and 10 women; 39 ± 4 years; 3 h 35 min ± 21 min). The day before the race, within 15 min after finishing the marathon and at 24, 48, 96, 144 and 192 h postrace, lactate dehydrogenase and creatine kinase were analysed. Participants also performed a squat jump (SJ) test before and after the marathon and at 48, 96 and 144 h postrace. On their arrival to the finish line, participants were randomized into one of the three intervention groups: running (RUN), elliptical training (ELIP) and resting recovery (REST). RUN and ELIP groups exercised continuously for 40 min at a moderate intensity (95-105% of the HR corresponding to the first ventilatory threshold) at 48, 96 and 144 h after the marathon. Neither 'Intervention' factor nor 'Intervention x Time' interaction effects were revealed for muscle damage blood markers (p > 0.05). On the other hand, RUN group evidenced an enhancement in SJ performance 96 h post-marathon as compared with REST group (108.29 ± 10.64 vs 100.58 ± 9.16%, p = 0.020, d = 0.80). Consequently, return to running at 48 h post-marathon does not seem to have a negative impact on muscle damage recovery up to eight days post-race and it could be recommended in order to speed up neuromuscular recovery.

RETRACTED: Anesthesic and surgical guideline for the treatment of the thoraco-abdominal aorta. Consensus Document of the Spanish Societies of Anesthesia and Cardiovascular Surgery. / Guía anestésico-quirúrgica en el tratamiento de la patología de aorta toracoabdominal. Documento de Consenso de la Sociedad Española de Cirugía Cardiovascular Endovascular y la Sociedad Española de Anestesiología, Reanimación y Terapeútica del Dolor.

Este artículo ha sido retirado por indicación del Editor Jefe de la revista, después de constatar que parte de su contenido había sido plagiado, sin mencionar la fuente original: European Heart Journal (2014) 35, 2873 926.: https://academic.oup.com/eurheartj/article/35/41/2873/407693#89325738 El autor de correspondencia ha sido informado de la decisión y está de acuerdo con la retirada del artículo. El Comité Editorial lamenta las molestias que esta decisión pueda ocasionar. Puede consultar la política de Elsevier sobre la retirada de artículos en https://www.elsevier.com/about/our-business/policies/article-withdrawal

Anaesthetic-surgical guide in the treatment of ascending aorta and surgery of the ascending aorta and aortic arch. Consensus document of the Spanish Society of Cardiovascular and Endovascular Surgery and the Sociedad of Anaesthesiology, Resuscitation and Pain Therapy. / Guía anestésico-quirúrgica en el tratamiento de la cirugía de aorta ascendente y del arco aórtico. Documento de consenso de la Sociedad Española de Cirugía Cardiovascular y Endovascular y la Sociedad Española de Anestesiología, Reanimación y Terapeútica del Dolor.

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

Magnetocaloric effect in magnetic nanoparticle systems: how to choose the best magnetic material?

Magnetic nanoparticles with controlled magnetocaloric properties are a good candidate to lower the temperature of nanosized systems: they are easy to manipulate and to distribute into different geometries, as wires or planes. Using a Monte Carlo technique we study the entropy change and refrigerant capacity of an assembly of fine magnetic particles as a function of their anisotropy and magnetization, key-parameters of the magnetic behavior of the system. We focus our attention on the anisotropy energy/dipolar energy ratio by means of the related parameter c0 = 2K/M(S)2, where K is the anisotropy constant and M(S) is the saturation magnetization of the nanoparticles. Making to vary the value of co parameter by choosing different K-M(S) combinations, allows us to discuss how the magnetocaloric response of an assembly of magnetic nanoparticles may be tuned by an appropriate choice of the magnetic material composition.

Thermal annealing dependence of high-frequency magnetoimpedance in amorphous and nanocrystalline FeSiBCuNb ribbons.

The magnetoimpedance (MI) effect in Fe73.5Si13.5B9Nb3Cu1 melt-spun amorphous ribbons has been studied in the frequency range (1-500 MHz). Isothermal heating treatments in a furnace have been employed to nanocrystallize the ribbons (1 h at 565 degrees C in a vacuum of 10(-3) mbar), while other samples were annealed at lower temperatures (400 and 475 degrees C during 1 h), in order to evaluate the influence of the annealing temperature on the MI effect. The high-frequency impedance was measured using a technique based on the reflection coefficient measurements of a specific transmission line by using a network analyzer. Frequency dependence of the MI ratio, DeltaZ/Z, and both resistive, DeltaR/R, and reactive, DeltaX/X, components of magnetoimpedance were measured in the amorphous and annealed states, at different temperatures. A maximum value of the MI ratio of about 50% at a driving frequency of 18 MHz is obtained in the nanocrystalline (annealed at 565 degrees C) ribbon. Maxima for DeltaR/R of about 81% at 85 MHz and DeltaX/X around 140% at 5 MHz were also achieved. It is revealed that the microstructural evolution in the nanocrystalline sample leads to a magnetic softening, an optimum domain structure and a permeability which is sensitive to frequency and applied magnetic field, generating a large MI response.

Loading dose of Dexdor® and optimal sedation during oral and maxillofacial ambulatory surgery procedures: An observational study. / Dosis de carga de Dexdor® y nivel óptimo de sedación durante procedimientos de cirugía oral y maxilofacial en régimen ambulatorio: un estudio observacional.

INTRODUCTION: Dexdor® do not include the possibility of loading dose, which could increase time to achieve adequate sedation for ambulatory procedures. The objective of this study was to evaluate the effect of several loading dose of dexmedetomidine in the time to achieve and maintain an optimal level of sedation and its clinical hemodynamic repercussion. MATERIAL AND METHODS: The IRB approved this observational study for patients that underwent oral and maxillofacial ambulatory surgery under dexmedetomidine at the University of Navarra Clinic from February 2013 to November 2014. According to the loading dose the patients were grouped into 3 categories:<0.5, 0.5, and>0.5µg/kg. Optimal level of sedation was defined as bispectral index<85. Data were analyzed using survival analysis techniques. Vasoactive drugs requirements was evaluated using exact logistic regression. RESULTS: Eighty-one patients were evaluated. Hazard ratios for patients in 0.5 and >0.5µg/kg loading dose categories for achieving a bispectral index<85 were 1.5 (95% CI 0.9, 2.6) and 1.8 (95% CI 0.8, 3.9), respectively, compared with the lowest category. Five patients (6.2%) required atropine for bradycardia. Patients in the group>0.5µg/kg showed greater risk of requiring atropine compared with the group<0.5µg/kg (odds ratio 2.2; 95% CI 0.03, 183). CONCLUSION: Loading dose of dexmedetomidine>0.5µg/kg appears minimize the time to achieve and maintain an optimal level of sedation during the first 60min of procedure. Further investigation to elucidate the association between loading dose of dexmedetomidine and subsequent atropine requirements may be warranted.

Ionic transport across tailored nanoporous anodic alumina membranes.

Highly ordered Nanoporous Alumina Membranes (NPAMs) with a precise control of the pore size and different porosity but thickness around 63 µm were fabricated by the two-step anodization process using different acidic aqueous solutions, oxalic (Al-Ox), sulfuric (Al-Sf), and phosphoric (Al-Ph) acids, respectively. The pore size was controlled by properly changing the anodization voltage and the electrochemical bath conditions, obtaining the following average pores diameter values, d(p), as determined by scanning electron micrographic analysis: Al-Ox (d(p)=46±2 nm), Al-Sf (d(p)=27±2 nm), and Al-Ph (d(p)=240±20 nm). A pore increasing of around 5% for samples Al-Ox and Al-Sf was obtained after membranes immersion in 5 wt.% phosphoric acid for a certain etching time. Electrochemical characterization of NPAMs was performed with the samples in contact with NaCl solutions at different electrolyte concentrations. Ionic transport numbers and effective membrane fixed charge were determined from membrane potential measurements, which clearly show the significant influence of the pore diameter on ions transport. Moreover, frictional and electrical effects on mass transfer parameters (salt and ions diffusion coefficients) into the pores of alumina membranes were also evaluated from these results.

Heterochronic events in the ontogeny of Columba livia, Coturnix coturnix, and Gallus gallus domesticus / Eventos heterocrónicos en la ontogenia de Columba livia, Coturnix coturnix y Gallus gallus domesticus / Eventos heterocrônicos na ontogenia da Columba livia, Coturnix coturnix e Gallus gallus domesticus

Summary Background: a series of events take place in a precise spatial and temporal context during the development of any organism. Typically, certain ontogenetic processes are consistent with the proper completion of previous events. Objective: to identify possible heterochronic events that may relate to altricial and precocious development patterns. Methods: we analyzed the ontogeny of three species of birds with two different development models: Columba livia (semialtricial 2), Coturnix coturnix, and Gallus gallus domesticus (precocial 2). The starts and endings of thirteen morphological events were compared, from hour 16 of incubation to the time of hatching. Results: while no differences in the sequence of developmental events were found, the events of the maturation stage in the altricial kind started earlier compared to the precocial species. Ontogenetic acceleration events in C. livia and C. coturnix explain how these species reach a level of morphological development similar to that of G. gallus domesticus, but with shorter incubation period. Conclusion: the results provide information not considered in the literature of the specialty about heterochronic events in early developmental stages of poultry.

Resumen Antecedentes: durante el desarrollo de cualquier organismo, tienen lugar una serie de eventos en un contexto espacial y temporal preciso. Comúnmente, ciertos procesos ontogenéticos son congruentes con la adecuada culminación de eventos previos. Objetivo: identificar posibles eventos heterocrónicos que pueden relacionarse con los patrones de desarrollo altriciales y precoces. Métodos: se analizó la ontogenia de tres especies de aves con dos modelos de desarrollo diferentes: Columba livia (semialtricial 2), Coturnix coturnix y Gallus gallus domesticus (precocial 2). Se comparó el inicio y la finalización de trece eventos morfogenéticos, desde las 16 h de incubación hasta el momento de la eclosión. Resultados: si bien no se observaron diferencias en la secuencia de eventos del desarrollo, en la especie altricial los eventos de maduración se iniciaron antes que en las especies precoces. La aceleración de eventos ontogenéticos en C. livia y C. coturnix explicaría cómo estas especies alcanzan un grado de desarrollo morfológico semejante al de G. gallus domesticus pero en un periodo de incubación menor. Conclusión: los resultados de este trabajo aportan información sobre eventos heterocrónicos en las etapas temprana del desarrollo de las aves, no consideradas en la literatura de la especialidad.

Resumo Antecedentes: durante o desenvolvimento de qualquer organismo ocorrem uma série de eventos num contexto espacial e temporal preciso. Comumente, certos processos ontogênicos são consistentes com a conclusão correta de eventos anteriores. Objetivo: identificar possíveis eventos heterocrônicos que podem estar relacionados a padrões de desenvolvimento altriciais e precoces. Métodos: Foi analisada a ontogenia de três espécies de aves com dois modelos diferentes de desenvolvimento: Columba livia (semialtricial 2), Coturnix coturnix e Gallus gallus domesticus (precoce 2). Foram comparados o início e o fim de treze eventos morfogenéticos, a partir das 16 h de incubação até a eclosão. Resultados: embora não foram observadas diferenças na sequência de eventos do desenvolvimento, na espécie altricial os eventos de maturação iniciaram-se mais cedo do que nas espécies precoces. A aceleração de eventos ontogênicos em C. coturnix C. livia pode explicar como essas espécies atingem um grau de desenvolvimento morfológico semelhante ao G. gallus domesticus em um período de incubação mais curto. Conclusão: os resultados deste estudo fornecem informação sobre eventos heterocrônicos nas fases iniciais do desenvolvimento das aves, não são considerados na literatura da especialidade.

Discrimination of complex visual stimuli in Cebus apella: identity matching with pictures

Do capuchin monkeys respond to photos as icons? Do they discriminate photos of capuchin monkeys’ faces? Looking for answers to these questions we trained three capuchin monkeys in simple and conditional discrimination tasks and tested the discriminations when comparison stimuli were partially covered. Three capuchin monkeys experienced in simultaneous simple discrimination and IDMTS were trained with repeated shifts of simple discriminations (RSSD), with four simultaneous choices, and IDMTS (1 s delay, 4 choices) with pictures of known capuchins monkeys’ faces. All monkeys did discriminate the pictures in both procedures. Performances in probes with partial masks with one fourth of the stimulus hidden were consistent with baseline level. Errors occurred when a picture similar to the correct one was available among the comparison stimuli, when the covered part was the most distinct, or when pictures displayed the same monkey. Capuchin monkeys do match pictures of capuchin monkeys’ faces to the sample. The monkeys treated different pictures of the same monkey as equivalent, suggesting that they respond to the pictures as icons, although this was not true to pictures of other monkeys. Subsequent studies may bring more evidence that capuchin monkeys treat pictures as depictions of real scenes.