Bioingeniería cutánea: aplicaciones preclínicas y clínicas

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering.Our work has been funded by the Spanish Department of Science and Innovation (SAF2007-61019 and SAF 2010-16976), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), and by the Ministry of Health (Advanced Therapies Plan, TRA 0160)

A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study

A new device for local delivery of antibiotics is presented, with potential use as a drug-eluting fixation pin for orthopedic applications. The implant consists of a stainless steel hollow tubular reservoir packed with the desired antibiotic. Release takes place through several orifices previously drilled in the reservoir wall, a process that does not compromise the mechanical properties required for the implant. Depending on the antibiotic chosen and the number of orifices, the release profile can be tailored from a rapid release of the load (ca. 20 h) to a combination of rapid initial release and slower, sustained release for a longer period of time (ca. 200 h). An excellent bactericidal action is obtained, with 4-log reductions achieved in as little as 2 h, and total bacterial eradication in 8 h using 6-pinholed implants filled with cefazolin

Genomic lineages of Rhizobium etli revealed by the extent of nucleotide polymorphisms and low recombination

<p>Abstract</p> <p>Background</p> <p>Most of the DNA variations found in bacterial species are in the form of single nucleotide polymorphisms (SNPs), but there is some debate regarding how much of this variation comes from mutation versus recombination. The nitrogen-fixing symbiotic bacteria <it>Rhizobium etli </it>is highly variable in both genomic structure and gene content. However, no previous report has provided a detailed genomic analysis of this variation at nucleotide level or the role of recombination in generating diversity in this bacterium. Here, we compared draft genomic sequences versus complete genomic sequences to obtain reliable measures of genetic diversity and then estimated the role of recombination in the generation of genomic diversity among <it>Rhizobium etli</it>.</p> <p>Results</p> <p>We identified high levels of DNA polymorphism in <it>R. etli</it>, and found that there was an average divergence of 4% to 6% among the tested strain pairs. DNA recombination events were estimated to affect 3% to 10% of the genomic sample analyzed. In most instances, the nucleotide diversity (π) was greater in DNA segments with recombinant events than in non-recombinant segments. However, this degree of recombination was not sufficiently large to disrupt the congruence of the phylogenetic trees, and further evaluation of recombination in strains quartets indicated that the recombination levels in this species are proportionally low.</p> <p>Conclusion</p> <p>Our data suggest that <it>R. etli </it>is a species composed of separated lineages with low homologous recombination among the strains. Horizontal gene transfer, particularly via the symbiotic plasmid characteristic of this species, seems to play an important role in diversity but the lineages maintain their evolutionary cohesiveness.</p

Synergistic assembly of gold and copper-iron oxide nanocatalysts to promote the simultaneous depletion of glucose and glutathione

Glucose and glutathione (GSH) are key biomolecules for the regulation and growth of tumor cells. The use of inorganic nanocatalysts in biomedicine to target and deplete such specific molecules represents a novel and promising strategy against cancer. In this work, we present a ternary assembled nanohybrid based on Au and CuFe2O4 with the capability to simultaneously deplete glucose and GSH and generate reactive oxidative species (ROS) in a cascade process. We describe an example of a synergistic heterogeneous nanoarchitecture able to maintain the glucose oxidase-like activity of Au while preventing its deactivation in the presence of GSH. Au sites remain active due to the rapid response of the Cu–Fe co-catalyst to deplete GSH levels. This example of hybrid heterostructure represents an appealing alternative with dual-activity within the tumor microenvironment (TME) for potential anticancer therapy

Brote nosocomial de COVID-19 en una planta de medicina interna: probable transmisión aérea

Transmissió aèria; Brot; COVID-19Transmisión aérea; Brote; COVID-19Airborne transmission; Outbreak; COVID-19Background and objectives: Despite the increasing evidence supporting the importance of airborne transmission in SARS-CoV-2 infection, it has not been considered relevant in the vast majority of reported nosocomial outbreaks of COVID-19. The aim of this study is to describe a nosocomial outbreak of SARS-CoV-2 infection whose features suggest that aerosol transmission had an important role. Methods: This is a descriptive analysis of a nosocomial outbreak of SARS-CoV-2 infection in an internal medicine ward that occurred in December 2020. All cases were confirmed by a positive PCR test for SARS-CoV-2. Results: From December 5 to December 17, 21 patients and 44 healthcare workers (HCWs) developed a nosocomial SARS-CoV-2 infection. Fifty-one of the 65 cases (78.5%) were diagnosed between December 6 and 9. The attack rate in patients was 80.8%. Among HCWs, the attack rate was higher in those who had worked at least one full working day in the ward (56.3%) than in those who had occasionally been in the ward (25.8%; p = 0.005). Three days before the first positive case was detected, two extractor fans were found to be defective, affecting the ventilation of three rooms. Sixteen cases were asymptomatic, 48 cases had non-severe symptoms, and 2 cases required admission to the intensive care unit. All patients eventually recovered. Conclusion: The high attack rate, the explosive nature of the outbreak, and the coincidence in time with the breakdown in air extractors in some rooms of the ward suggest that airborne transmission played a key role in the development of the outbreak.Antecedentes y objetivos A pesar de los datos cada vez mayores que respaldan la importancia de la transmisión aérea en la infección por el SARS-CoV-2, en la inmensa mayoría de los brotes nosocomiales descritos de COVID-19 no se ha considerado relevante. El objetivo de este estudio consiste en describir un brote nosocomial de infección por el SARS-CoV-2 cuyas características indican que la transmisión por aerosoles desempeñó un papel importante. Métodos Se trata de un análisis descriptivo de un brote nosocomial de infección por el SARS-CoV-2 en una planta de Medicina Interna que tuvo lugar en diciembre de 2020. Todos los casos se confirmaron mediante una PCR positiva para SARS-CoV-2. Resultados Entre el 5 y el 17 de diciembre, 21 pacientes y 44 profesionales sanitarios contrajeron una infección nosocomial por el SARS-CoV-2. De los 65 casos, 51 (78,5%) se diagnosticaron entre el 6 y el 9 de diciembre. La tasa de ataque en los pacientes fue del 80,8%. Entre los profesionales sanitarios, la tasa de ataque fue mayor en los que habían trabajado al menos una jornada laboral completa en la planta (56,3%) que en los que habían estado ocasionalmente en ella (25,8%; p = 0,005). Tres días antes de detectar el primer caso positivo se identificó una avería en dos extractores de aire, que afectó a la ventilación de tres habitaciones. Dieciséis casos cursaron de forma asintomática, 48 manifestaron síntomas leves y 2 precisaron ingreso en la unidad de cuidados intensivos. Todos los casos se recuperaron finalmente. Conclusiones La elevada tasa de ataque, la naturaleza explosiva del brote y la coincidencia en el tiempo con la avería de los extractores de aire en algunas habitaciones de la planta indican que la transmisión aérea desempeñó un papel fundamental en el desarrollo del brote

Enhanced asymmetrical modulation for half-bridge series resonant inverters in induction heating applications

This paper presents a method that improves the reliability of half-bridge (HB) series resonant inverters (SRI) for high-frequency induction heating applications. Many industrial processes, like induction heat treatments, are very repetitive. This cyclical operation represents a strong limitation of the inverter's reliability, mainly due to the accelerated stress of the power semiconductors. This method consists in an enhanced asymmetrical pulse width modulation (EAPWM) that allows distributing the losses across the components, thereby reducing the cyclic increase in junction temperature of the power devices, and thus achieves a reliability that is more than twice as high as that achieved using traditional modulation methods. The work methodology includes a theoretical study of the HB inverter and a complete analysis of losses. The presented design rules have been used to implement a 25 kW, 100 kHz inverter. The use of silicon carbide (SiC) MOSFET transistors allows reaching an efficiency greater than 99%. The analytical results obtained have been experimentally validated by testing the inverter on an induction heating test bench

High-pressure study of the behavior of mineral barite by X-ray diffraction

In this paper, we report the angle-dispersive x-ray diffraction data of barite, BaSO 4, measured in a diamond-anvil cell up to a pressure of 48 GPa, using three different fluid pressure-transmitting media (methanol-ethanol mixture, silicone oil, and He). Our results show that BaSO 4 exhibits a phase transition at pressures that range from 15 to 27 GPa, depending on the pressure media used. This indicates that nonhydrostatic stresses have a crucial role in the high-pressure behavior of this compound. The new high-pressure (HP) phase has been solved and refined from powder data, having an orthorhombic P2 12 12 1 structure. The pressure dependence of the structural parameters of both room- and HP phases of BaSO 4 is also discussed in light of our theoretical first-principles total-energy calculations. Finally, a comparison between the different equations of state obtained in our experiments is reported. © 2011 American Physical Society.Financial support from the Spanish Consolider Ingenio 2010 Program (Project No. CDS2007-00045) is acknowledged. The work was also supported by Spanish MICCIN under Projects No. CTQ2009-14596-C02-01 and No. MAT2010-21270-C04-01 as well as from Comunidad de Madrid and European Social Fund: S2009/PPQ-1551 4161893 (QUIMAPRES). The ESRF is acknowledged for provision of beamtime.Santamaría-Pérez, D.; Gracia, L.; Garbarino, G.; Beltrán, A.; Chuliá-Jordán, R.; Gomis Hilario, O.; Errandonea, D.... (2011). High-pressure study of the behavior of mineral barite by X-ray diffraction. Physical Review B. 84:54102-1-54102-8. https://doi.org/10.1103/PhysRevB.84.054102S54102-154102-884RUBIN, A. E. (1997). Mineralogy of meteorite groups. Meteoritics & Planetary Science, 32(2), 231-247. doi:10.1111/j.1945-5100.1997.tb01262.xVegas, A. (2000). Cations in Inorganic Solids. Crystallography Reviews, 7(3), 189-283. doi:10.1080/08893110008044245Santamaría-Pérez, D., & Vegas, A. (2003). The Zintl–Klemm concept applied to cations in oxides. I. The structures of ternary aluminates. Acta Crystallographica Section B Structural Science, 59(3), 305-323. doi:10.1107/s0108768103005615Vegas, A., & Jansen, M. (2001). Structural relationships between cations and alloys; an equivalence between oxidation and pressure. Acta Crystallographica Section B Structural Science, 58(1), 38-51. doi:10.1107/s0108768101019310Lee, P.-L., Huang, E., & Yu, S.-C. (2001). Phase diagram and equations of state of BaSO4. High Pressure Research, 21(2), 67-77. doi:10.1080/08957950108201005Lee, P.-L., Huang, E., & Yu, S.-C. (2003). High-pressure Raman and X-ray studies of barite, BaSO4. High Pressure Research, 23(4), 439-450. doi:10.1080/0895795031000115439Crichton, W. A., Merlini, M., Hanfland, M., & Muller, H. (2011). The crystal structure of barite, BaSO4, at high pressure. American Mineralogist, 96(2-3), 364-367. doi:10.2138/am.2011.3656Errandonea, D., Santamaria-Perez, D., Bondarenko, T., & Khyzhun, O. (2010). New high-pressure phase of HfTiO4 and ZrTiO4 ceramics. Materials Research Bulletin, 45(11), 1732-1735. doi:10.1016/j.materresbull.2010.06.061López-Solano, J., Rodríguez-Hernández, P., Muñoz, A., Gomis, O., Santamaría-Perez, D., Errandonea, D., … Raptis, C. (2010). Theoretical and experimental study of the structural stability ofTbPO4at high pressures. Physical Review B, 81(14). doi:10.1103/physrevb.81.144126Hammersley, A. P., Svensson, S. O., Hanfland, M., Fitch, A. N., & Hausermann, D. (1996). Two-dimensional detector software: From real detector to idealised image or two-theta scan. High Pressure Research, 14(4-6), 235-248. doi:10.1080/08957959608201408Mao, H. K., Xu, J., & Bell, P. M. (1986). Calibration of the ruby pressure gauge to 800 kbar under quasi-hydrostatic conditions. Journal of Geophysical Research, 91(B5), 4673. doi:10.1029/jb091ib05p04673Rodríguez-Carvajal, J. (1993). Recent advances in magnetic structure determination by neutron powder diffraction. Physica B: Condensed Matter, 192(1-2), 55-69. doi:10.1016/0921-4526(93)90108-iBecke, A. D. (1993). Density‐functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics, 98(7), 5648-5652. doi:10.1063/1.464913Lee, C., Yang, W., & Parr, R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37(2), 785-789. doi:10.1103/physrevb.37.785Gracia, L., Beltrán, A., & Andrés, J. (2007). Characterization of the High-Pressure Structures and Phase Transformations in SnO2. A Density Functional Theory Study. The Journal of Physical Chemistry B, 111(23), 6479-6485. doi:10.1021/jp067443vGracia, L., Beltrán, A., & Errandonea, D. (2009). Characterization of theTiSiO4structure and its pressure-induced phase transformations: Density functional theory study. Physical Review B, 80(9). doi:10.1103/physrevb.80.094105Blanco, M. A., Francisco, E., & Luaña, V. (2004). GIBBS: isothermal-isobaric thermodynamics of solids from energy curves using a quasi-harmonic Debye model. Computer Physics Communications, 158(1), 57-72. doi:10.1016/j.comphy.2003.12.001Errandonea, D., Santamaría-Perez, D., Vegas, A., Nuss, J., Jansen, M., Rodríguez-Hernandez, P., & Muñoz, A. (2008). Structural stability ofFe5Si3andNi2Sistudied by high-pressure x-ray diffraction andab initiototal-energy calculations. Physical Review B, 77(9). doi:10.1103/physrevb.77.094113Santamarı́a-Pérez, D., Nuss, J., Haines, J., Jansen, M., & Vegas, A. (2004). Iron silicides and their corresponding oxides: a high-pressure study of Fe5Si3. Solid State Sciences, 6(7), 673-678. doi:10.1016/j.solidstatesciences.2004.03.027Errandonea, D., Meng, Y., Somayazulu, M., & Häusermann, D. (2005). Pressure-induced transition in titanium metal: a systematic study of the effects of uniaxial stress. Physica B: Condensed Matter, 355(1-4), 116-125. doi:10.1016/j.physb.2004.10.030Klotz, S., Paumier, L., Le March, G., & Munsch, P. (2009). The effect of temperature on the hydrostatic limit of 4:1 methanol–ethanol under pressure. High Pressure Research, 29(4), 649-652. doi:10.1080/08957950903418194Errandonea, D., & Manjón, F. J. (2008). Pressure effects on the structural and electronic properties of ABX4 scintillating crystals. Progress in Materials Science, 53(4), 711-773. doi:10.1016/j.pmatsci.2008.02.001Lacomba-Perales, R., Errandonea, D., Meng, Y., & Bettinelli, M. (2010). High-pressure stability and compressibility ofAPO4(A=La, Nd, Eu, Gd, Er, and Y) orthophosphates: An x-ray diffraction study using synchrotron radiation. Physical Review B, 81(6). doi:10.1103/physrevb.81.064113Crichton, W. A., Parise, J. B., Antao, S. M., & Grzechnik, A. (2005). Evidence for monazite-, barite-, and AgMnO4(distorted barite)-type structures of CaSO4at high pressure and temperature. American Mineralogist, 90(1), 22-27. doi:10.2138/am.2005.1654Huang, T., Shieh, S. R., Akhmetov, A., Liu, X., Lin, C.-M., & Lee, J.-S. (2010). Pressure-induced phase transition inBaCrO4. Physical Review B, 81(21). doi:10.1103/physrevb.81.214117Zhang, F. X., Wang, J. W., Lang, M., Zhang, J. M., Ewing, R. C., & Boatner, L. A. (2009). High-pressure phase transitions ofScPO4andYPO4. Physical Review B, 80(18). doi:10.1103/physrevb.80.184114Panchal, V., Garg, N., & Sharma, S. M. (2006). Raman and x-ray diffraction investigations on BaMoO4under high pressures. Journal of Physics: Condensed Matter, 18(16), 3917-3929. doi:10.1088/0953-8984/18/16/00