Cell biophysical stimuli in lobodopodium formation: a computer based approach

Different cell migration modes have been identified in 3D environments, e.g., modes incorporating lamellopodia or blebs. Recently, a new type of cellular migration has been investigated: lobopodia-based migration, which appears only in three-dimensional matrices under certain conditions. The cell creates a protrusion through which the nucleus slips, dividing the cell into two parts (front and rear) with different hydrostatic pressures. In this work, we elucidate the mechanical conditions that favour this type of migration. One of the hypotheses about this type of migration is that it depends on the mechanical properties of the extracellular matrix. That is, lobopodia-based migration is dependent on whether the extracellular matrix is linearly elastic or non-linearly elastic. To determine whether the mechanical properties of the extracellular matrix are crucial in the choice of cell migration mode and which mechanotransduction mechanism the cell might use, we develop a finite element model. From our simulations, we identify two different possible mechanotransduction mechanisms that could regulate the cell to switch from a lobopodial to a lamellipodial migration mode. The first relies on a differential pressure increase inside the cytoplasm while the cell contracts, and the second relies on a change in the fluid flow direction in non-linearly elastic extracellular matrices but not in linearly elastic matrices. The biphasic nature of the cell has been determined to mediate this mechanism and the different behaviours of cells in linearly elastic and non-linearly elastic matrices

Finite Element Simulation of the Deformation of a Cell Driven by Creeping Flow

The purpose of this work is to calculate the deformation undergone by a cell in function of its nucleus size and mechanical properties. The cell immersed in a fluid go through a variable section channel and it is deformed by fluid forces.Cell deformation into the channel causes changes at the fluid velocity profile. This fluid configuration change results in diferent normal and viscous forces around the cell. Due to strong correlation between cell deformation and fluid velocity profile, a fluidsolid interacción (FSI) is required

Resolución de enigmas geológicos e históricos utilizando técnicas gemológicas avanzadas: Caso del ópalo noble de Franco Dávila (1772)

The large precious opal weighting 33 grams fitted in a silver jewel and exposed to visitors at the Museo Nacional de Ciencias Naturales (MNCN) is well documented in: (i) its own mounting (1772), (ii) at the 775 document of the Archive of the MNCN and (iii) the 395 specimen described in the of Pedro Franco Dávila catalogue. The X-ray diffractogram (XRD) performed onto the opal block is very similar to other opals of volcanic origin containing varied amounts of cristobalite, tridymite and amorphous silica. The Raman spectrum shows a band peaked at 242, 343 and 416 cm-1 associated with O-Si-O stretching groups; other spectral band peaked at 780 and 819 cm-1 corresponding to vibration of symmetrical O-Si-O rings of 3 and 4 link members, plus other minor bands. The Raman spectrum is also very similar to those observed in Mexican opals of volcanic origin containing an spectral band of stretching nodes v1 (OH) at 3233, 3393, 3511, 3628 cm-1 related to OH groups with hydrogen bonds of isolated silanol groups. The interferometric confocal dual microscope 3D (MCI3D), which is a nondestructive facility of high resolution and LED technology reveals the geometry of graver tools on the silver jewel and the computed tomography X-ray highlights the opal cutting as a squared princess type and silver chloride infillings of a crack probably caused by a shock on a corner. Under the scanning electron microscope we observed barite, sealed veins of silica rich in Mn and opal with high contents of Al and K which, along with the historical data, the piece can be attributed to the historical site of opals hosted in Slovakia andesite rocks, this data explains the optical light behavior in the cabochon. The silver jewel has large amounts of Hg and AgCl indicating amalgam method. In addition the natural AgS2 phases probably come from Nueva España (year 1772) in full production of silver in such time. The association of new analytical non-destructive techniques combines the preservation of samples together with significant analytical data allowing us to deduce genetic mineral processes, provenances and manufacturing techniques of materials. These facilities allow the characterization, interpretation, conservation and enhancement of cultural and archaeological heritage.Un gran ópalo noble de 33 gramos engastado en montura de plata dorada está expuesto al público en el Museo Nacional de Ciencias Naturales (MNCN). Esta pieza histórica está documentada en su propia montura (año 1772), en el legajo 775 del Archivo del Museo y en la muestra 395 del Catálogo de muestras de Pedro Franco Dávila. Su patrón de difracción de rayos X (DRX) es muy parecido al de otros ópalos de origen volcánico y contiene cantidades variables de cristobalita, tridimita y sílice amorfa. El espectro Raman muestra una banda con picos a 242, 343 y 416 cm-1 asociados a deformaciones O-Si-O; otra con picos a 780 y 819 cm-1 de vibraciones de tensión simétricas O-Si-O de anillos de 3 y 4 eslabones y otras menores. El espectro Raman es similar a los de ópalos mexicanos de origen volcánico y muestra una banda con nodos de tensión v1 (OH) a 3233, 3393, 3511, 3628 cm-1 relacionados con grupos OH con enlaces de hidrógeno con grupos silanoles aislados. Mediante microscopía dual confocal interferométrica 3D (MCI3D), que es una técnica no destructiva de alta resolución y tecnología LED, se desvela la geometría de grabado del buril sobre la montura mientras que la tomografía computerizada de rayos X destaca la talla cuadrada de tipo carre-princesa y los rellenos de AgCl de una fisura. Bajo microscopia electrónica de barrido ambiental (MEBA) se han observado baritinas, filoncillos de sílice enriquecida en Mn y elevados contenidos de Al y K. Estos datos, junto con la información histórica sugieren que la pieza procede de los yacimientos históricos de ópalos encajados en andesitas de Eslovaquia y explican la compleja óptica del cabujón. El marco de Ag tiene Hg y AgCl que indican su extracción por amalgama; además tiene Ag2S que podría provenir de Nueva España, entonces (año 1772) en plena producción de plata. La asociación de varias técnicas analíticas no-destructivas preserva la integridad de esta pieza histórica aportando datos analíticos significativos que permiten deducir procesos genéticos de minerales, procedencias y técnicas de manufactura de materiales. Todo ello facilita la caracterización, interpretación, conservación y valorización del patrimonio cultural y arqueológico

Congenital long QT syndrome

Artículo especialThe long QT syndrome (LQTS) is an hereditary disease that produces a malfunction on the sodium and potassium channels of the heart and lengthens the duration of the cardiac repolarization stage. It is characterized by the appearance of syncopes, arrhythmias and even sudden death. There are two variants of the congenital LQTS: the autosomal dominant Romano-Ward syndrome and the autosomal recessive Jervell-Lange-Nielsen syndrome, that is associated with sensorineural deafness and is less frequent than the other type. The diagnosis is made from the clinical criteria, the electrocardiogram and the family history. In the last few years, molecular studies have been developed, opening new possibilities not only for its diagnosis but also for the treatment of these patients.N

Non-alcoholic fatty liver in hereditary fructose intolerance

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2 . The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-L-homocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients : Protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

Altres ajuts: The BEATLE study is a non-commercial, investigator-driven clinical trial funded by the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005; RD16/0016/0010) The Spanish Clinical Research Network (SCReN) provides clinical trial data monitoring and oversees pharmacovigilance (PT17/0017/0010).Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. Discussion: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. Trial registration: European Clinical Trials Database: EudraCT 2018-001476-37. ClinicalTrials.gov, ID: NCT04233996

Contribución de la Paleofitogeografía a la interpretación del paisaje vegetal ibérico: estado de conocimientos y nuevas perspectivas de investigación

The palaeobotanical studies that have been accomplished in the Iberian Peninsula during the last two decades have provided a great amount of data that can be applied in geobotanical knowledge. In most of the cases, those results have contributed to solve classical scientific debates regarding vegetal landscapes interpretations. One of the most relevant discussions is related to the aloctonous or non-aloctonous origin of much of the Iberian pine forests, on diverse Iberian habitats. The main contributions of Palaeobotany to the processes that explain the present distribution of plants are reviewed in a spatial and temporal framework, from old geological periods (Mesozoic, Tertiary) to the recent ones (Pleistocene, Holocene). Linked to the history of our vegetal landscapes, Pleistocene and Holocene epochs have been treated from two different points of view: firstly the problems within extensive territorial environments and, secondly, the problems related to the interpretation of the evolution and/or behaviour of taxa. In the last part, some new investigation trends related to palaeophytogeography are exposed, focusing on the high potential interest on being applied to Iberian ecosystems.Los trabajos de carácter paleobotánico realizados en la península Ibérica en las dos últimas décadas han proporcionado un importante volumen de resultados con aplicación en el ámbito del conocimiento geobotánico. En muchos casos, esos resultados han aportado soluciones a debates clásicos relativos a la interpretación del paisaje vegetal. Uno de los más conocidos es el de la consideración, como espontáneos o no, de muchos de los pinares ibéricos en diferentes ámbitos del territorio peninsular. Se revisan las contribuciones más importantes de la Paleobotánica a los procesos que explican la actual distribución de las plantas, en un marco tanto espacial como temporal, desde periodos geológicos antiguos (Mesozoico, Terciario) a los más recientes (Pleistoceno, Holoceno). Dentro de estos últimos nos hemos referido, por una parte, a problemas planteados en ámbitos territoriales extensos y, por otra, a problemas vinculados a la interpretación de la evolución y/o comportamiento de taxones concretos. Por último se hace referencia a las tendencias recientes y nuevas metodologías de aplicación en paleofitogeografía, aludiendo a los primeros resultados que hayan podido proporcionar en el marco peninsular

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: Outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database

Background: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. Methods: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. Results: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. Conclusions: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely

Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016)

La diseminación mundial de Staphylococcus aureus resistente a meticilina (SARM) está asociada a la aparición y el establecimiento de clones en zonas geográficas específicas. El clon chileno-cordobés (ChC) (ST5-SCCmecI) ha sido el clon de SARM predominante en Chile desde su primera descripción en 1998, a pesar del informe de otros clones de SARM emergentes en los últimos años. Aquí, caracterizamos la historia evolutiva de MRSA desde 2000 hasta 2016 en un centro de salud terciario chileno utilizando análisis filogenómicos. Secuenciamos 469 aislamientos de SARM recogidos entre 2000 y 2016. Evaluamos las tendencias temporales de los clones circulantes y realizamos una reconstrucción filogenómica para caracterizar la dinámica clonal. Encontramos un aumento significativo en la diversidad y riqueza de tipos de secuencia (STs; Spearman r = 0,8748, P , 0,0001) con un índice de diversidad de Shannon que aumentó de 0,221 en el año 2000 a 1,33 en 2016, y una diversidad efectiva (número de Hill; q = 2) que aumentó de 1,12 a 2,71. El análisis de la tendencia temporal reveló que en el periodo de 2000 a 2003 la mayoría de los aislados (94,2%; n = 98) pertenecían al clon ChC. Sin embargo, desde entonces, la frecuencia del clon ChC ha disminuido con el tiempo, representando el 52% de la colección en el período de 2013 a 2016. Este descenso estuvo acompañado por el aumento de dos linajes emergentes de SARM, ST105-SCCmecII y ST72-SCCmecVI. En conclusión, el clon ChC sigue siendo el linaje MRSA más frecuente, pero este linaje está siendo reemplazado gradualmente por varios clones emergentes, el más importante de los cuales es el clon ST105-SCCmecII. Hasta donde sabemos, éste es el mayor estudio de la dinámica clonal del SARM realizado en Sudamérica. © 2023 Martínez et al.The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P , 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. © 2023 Martínez et al

Nuevos datos de carbones y maderas fósiles de Pinus pinaster Aiton en el Holoceno de la Península Ibérica

The study of ligneous fossil remains (charcoal and wood) corresponding to three sites located in the interior of the Iberian Peninsula is presented. The chronologies established by means of radiocarbon or relative dating (archaeological) situate all the samples in the last phase of the Holocene. In the three deposits Pinus pinaster has been identified and there have being made other taxonomic contributions. A review of previous Pinus pinaster findings registered in the Peninsula is exposed and other considerations are made on the importance of this taxon in the Iberian vegetal landscape during the end of the Quaternary.Se ha realizado un estudio de restos fósiles leñosos correspondientes a tres yacimientos del interior de la península Ibérica: Hontalbilla (Segovia), Yecla (Murcia) y Castillejos (Badajoz). Las cronologías establecidas mediante datación absoluta (radiocarbono) o relativa (arqueológica) sitúan todas las muestras en la última fase del Holoceno. En los tres yacimientos se ha identificado Pinus pinaster, realizándose además otras aportaciones taxonómicas. Se reúnen los datos conocidos de macrorrestos de P. pinaster registrados en la Península y se realizan consideraciones sobre la importancia de este taxon en el paisaje vegetal ibérico durante el final del Cuaternario