Effects of Rho kinase inhibitors on grafts of dopaminergic cell precursors in a rat model of Parkinson's Disease

In models of Parkinson’s disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axonstabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PDThis work was supported by Spanish Ministry of Health (PI12/00798 and RD12/0019/0020) and Spanish Ministry of Economy and Competitiveness (BFU2012-3708)S

Análisis molecular de la resistencia a la polimixina en Klebsiella pneumoniae productora de carbapenemasas en Colombia

La resistencia a la polimixina en Klebsiella pneumoniae se ha atribuido a mutaciones en mgrB, phoPQ, pmrAB y crrAB y a la presencia de genes mediados por plásmidos mcr. En este trabajo se describen las características moleculares de 24 aislamientos de K. pneumoniae resistentes a polimixina y carbapenem recuperados en seis ciudades colombianas entre 2009 y 2019. Las concentraciones inhibitorias mínimas (CIM) a la polimixina se confirmaron por microdilución en caldo, y se realizó la secuenciación del genoma completo para determinar el tipo de secuencia, el resistoma y las mutaciones en los genes relacionados con la resistencia a la polimixina, así como la presencia de mcr. Los resultados mostraron una resistencia de alto nivel a la polimixina (CMI _ 4 _g/mL). blaKPC-3 estaba presente en la mayoría de los aislados (17/24; 71%), seguido de blaKPC-2 (6/24; 25%) y blaNDM-1 (1/24; 4%). La mayoría de los aislados pertenecían al CG258 (17/24; 71%) y presentaban sustituciones de aminoácidos en PmrB (22/24; 92%) y CrrB (15/24; 63%); las mutaciones en mgrB sólo se produjeron en cinco aislados (21%). No se identificaron mutaciones adicionales en pmrA, crrA y phoPQ ni en ninguno de los genes de resistencia mcr. En conclusión, se encontró diseminación clonal de aislamientos de K. pneumoniae resistentes a polimixina y carbapenemes en Colombia, principalmente asociados con CG258 y blaKPC-3. La vigilancia de esta bacteria multirresistente a fármacos se ha llevado a cabo en Colombia. La vigilancia de este clon multirresistente se justifica debido a las limitadas opciones terapéuticas para el tratamiento de las infecciones por K. pneumoniae resistente a carbapenemes.Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs _ 4 _g/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenemresistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections

Understanding bottom-up continuous hydrothermal synthesis of nanoparticles using empirical measurement and computational simulation

Continuous hydrothermal synthesis was highlighted in a recent review as an enabling technology for the production of nanoparticles. In recent years, it has been shown to be a suitable reaction medium for the synthesis of a wide range of nanomaterials. Many single and complex nanomaterials such as metals, metal oxides, doped oxides, carbonates, sulfides, hydroxides, phosphates, and metal organic frameworks can be formed using continuous hydrothermal synthesis techniques. This work presents a methodology to characterize continuous hydrothermal flow systems both experimentally and numerically, and to determine the scalability of a counter current supercritical water reactor for the large scale production (>1,000 T·year–1) of nanomaterials. Experiments were performed using a purpose-built continuous flow rig, featuring an injection loop on a metal salt feed line, which allowed the injection of a chromophoric tracer. At the system outlet, the tracer was detected using UV/Vis absorption, which could be used to measure the residence time distribution within the reactor volume. Computational fluid dynamics (CFD) calculations were also conducted using a modeled geometry to represent the experimental apparatus. The performance of the CFD model was tested against experimental data, verifying that the CFD model accurately predicted the nucleation and growth of the nanomaterials inside the reactor

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

Purpose: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg 21; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, doubleblind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75 % 1RM load) and muscle power adaptations (1 m s 21 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOK LEG) were measured to identify caffeine’s action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85 % 1RM) 6 repetitions bout of SQ (POST). Results: In the PM PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM PLA

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Intelligent Electronic System to Control the Interconnection between Distributed Generation Resources and Power Grid

[ES] Las transformaciones que están teniendo lugar en el sector eléctrico están haciendo evolucionar la red hacia un modelo más inteligente y eficiente conocido como Smart Grid. En este contexto, a los DERs que se integren en la red se les requerirá un control avanzado de la interfaz de conexión. Este trabajo presenta un original dispositivo electrónico inteligente (IED) de altas prestaciones para el control de la interconexión eléctrica con numerosas y nuevas prestaciones. El dispositivo tiene sobrada capacidad para contemplar tanto la calidad de suministro como operar multifuncionalmente a nivel de protección y seguridad; y su arquitectura modular en un Sistema Embebido permite una fácil integración, tanto en el desarrollo de equipos de nueva generación, como en equipamiento convencional ya instalado para adaptarlo al nuevo contexto de gestión inteligente. Se ha desarrollado un IED que ha sido sometido a pruebas de clase A siguiendo la normativa IEC 61000-4-30 e IEC 62586-2, y se le han efectuado ensayos para validar la respuesta temporal en la generación de órdenes y señales de alarma para protecciones. Se muestran y analizan algunos de estos resultados experimentales, y se comenta la experiencia de integración real de este prototipo en un inversor inteligente experimental, diseñado expresamente para operar en un escenario Smart Grid.[EN] The changes that are taking place in the electricity sector are causing an evolution of grid towards a more intelligent and efficient model known as Smart Grid. In this context equipment that connect to electric system require an intelligent control of the connection interface. This paper presents the design and development of an intelligent electronic device (IED) with high performance for controlling the electrical interconnection. The device has multifunctional ability to analyze power quality and operate with protections, and its modular architecture allows easy integration in both the development of next generation equipment, as in conventional equipment already installed to adapt to the new context of intelligent management. It has developed a prototype that has been tested with A class tests following the standards IEC 61000-4-30 and IEC 62586-2, and we have performed tests to validate the time response in generating orders and alarm signals for protections. Are shown and discussed some of these experimental results and the experience of integration of this prototype in an experimental smart inverter that is designed to operate in a Smart Grid scenario.Este trabajo ha sido posible gracias a la financiación del Ministerio de Ciencia e Innovación de España, en el ámbito del proyecto nacional de investigación denominado SIDER (Smart Inverter for Distributed Energy Resources) con código de contrato TEC2010 19242-C03-02.Real Calvo, R.; Moreno Muñoz, A.; Pallares López, V.; González Redondo, MJ.; Moreno García, IM.; Palacios García, EJ. (2017). Sistema Electrónico Inteligente para el Control de la Interconexión entre Equipamiento de Generación Distribuida y la Red Eléctrica. Revista Iberoamericana de Automática e Informática industrial. 14(1):56-69. https://doi.org/10.1016/j.riai.2016.11.002OJS5669141Abbey, C., Brissette, Y., Lemire, R., Zavoda, F., 2013. Universal IED for distribution smart grids, in: 22nd International Conference and Exhibition on Electricity Distribution (CIRED 2013). Institution of Engineering and Technology, pp. 0863-0863. doi:10.1049/cp.2013.0976Agüera-Pérez, A., Carlos Palomares-Salas, J., De La Rosa, J.J.G., María Sierra-Fernández, J., Ayora-Sedeño, D., Moreno-Muñoz, A., 2011. Characterization of electrical sags and swells using higher-order statistical estimators. Meas. J. Int. Meas. Confed. 44, 1453-1460.Angelino de Souza, W., Pinhabel Marafao, F., Verri Liberado, E., Severino Diniz, I., Amaral Serni, P.J., 2015. Power Quality, Smart Meters and Additional Information from Different Power Terms. IEEE Lat. Am. Trans. 13, 158-165. doi:10.1109/TLA.2015.7040643Benoit, C., Mercier, A., Besanger, Y., Wurtz, F., 2013. Deterministic optimal power flow for smart grid short-term predictive energy management, in: 2013 IEEE Grenoble Conference. IEEE, pp. 1-7. doi:10.1109/PTC.2013.6652502Bower, W., Ropp, M., 2002. Evaluation of Islanding Detection Methods for Utility-Interactive Inverters in Photovoltaic Systems (Report). Sandia National Laboratories.Brown, H.E., Suryanarayanan, S., Heydt, G.T., 2010. Some characteristics of emerging distribution systems considering the smart grid initiative. Electr. J. 23, 64-75.Caruana, C., Sattar, A., Al-Durra, A., Muyeen, S.M., 2015. Real-time testing of energy storage systems in renewable energy applications. Sustain. Energy Technol. Assessments 12, 1-9. doi:10.1016/j.seta.2015.08.001Colak, I., Fulli, G., Sagiroglu, S., Yesilbudak, M., Covrig, C.-F., 2015a. Smart grid projects in Europe: Current status, maturity and future scenarios. Appl. Energy 152, 58-70. doi:10.1016/j.apenergy.2015.04.098Colak, I., Kabalci, E., Fulli, G., Lazarou, S., 2015b. A survey on the contributions of power electronics to smart grid systems. Renew. Sustain. Energy Rev. 47, 562-579. doi:10.1016/j.rser.2015.03.031Dash, P.K., Padhee, M., Barik, S.K., 2012. Estimation of power quality indices in distributed generation systems during power islanding conditions. Int. J. Electr. Power Energy Syst. 36, 18-30. doi:10.1016/j.ijepes.2011.10.019De La Rosa, J.J.G., Moreno-Muñoz, A., Palomares, J.C., Agüera, A., 2010. Automatic classification of Power Quality disturbances via higher-order cumulants and self-organizing networks, in: 2010 IEEE International Symposium on Industrial Electronics, ISIE 2010. Bari, pp. 1579-1584.Deng, R., Yang, Z., Hou, F., Chow, M.-Y., Chen, J., 2015. Distributed RealTime Demand Response in Multiseller-Multibuyer Smart Distribution Grid. IEEE Trans. Power Syst. 30, 2364-2374. doi:10.1109/TPWRS.2014.2359457Dong Han, Zheng Yan, Yiqun Song, Libing Yang, Yuanrui Hong, 2014. A robust optimization approach to evaluate the impact of smart grid technologies on generation plans, in: 2014 International Conference on Power System Technology. IEEE, pp. 1706-1711. doi:10.1109/POWERCON.2014.6993510Gonzalez, E., Delgado, I., Monreal, J., Pazos, F.J., Romero-Cadaval, E., 2013. Failure analysis of inverter based anti-islanding systems in photovoltaic islanding events, in: 22nd International Conference and Exhibition on Electricity Distribution (CIRED 2013). Institution of Engineering and Technology, pp. 0558-0558. doi:10.1049/cp.2013.0800Gonzalez-Redondo, M.J., Moreno-Munoz, A., Pallares-Lopez, V., RealCalvo, R.J., 2016. Influence of data-related factors on the use of IEC 61850 for power utility automation. Electr. Power Syst. Res. 133, 269- 280. doi:10.1016/j.epsr.2015.12.028Heydt, G.T., 2010. The Next Generation of Power Distribution Systems. IEEE Trans. Smart Grid 1, 225-235. doi:10.1109/TSG.2010.2080328Jia, G., Taflanidis, A.A., 2015. Non-parametric stochastic subset optimization utilizing multivariate boundary kernels and adaptive stochastic sampling. Adv. Eng. Softw. 89, 3-16. doi:10.1016/j.advengsoft.2015.06.014Katiraei, F., Sun, C., Enayati, B., 2015. No Inverter Left Behind: Protection, Controls, and Testing for High Penetrations of PV Inverters on Distribution Systems. IEEE Power Energy Mag. 13, 43-49. doi:10.1109/MPE.2014.2380374Legarreta, A.E., Figueroa, J.H., Bortolin, J.A., 2011. An IEC 61000-4-30 class A - Power quality monitor: Development and performance analysis, in: 11th International Conference on Electrical Power Quality and Utilisation. IEEE, pp. 1-6. doi:10.1109/EPQU.2011.6128813Mahat, P., Chen, Z., Bak-Jensen, B., 2011. Review on islanding operation of distribution system with distributed generation, in: 2011 IEEE Power and Energy Society General Meeting. Detroit, MI, pp. 1-8.Radil, T., Ramos, P.M., 2010. Power quality detection and classification method for IEC 61000-4-30 Class A instruments, in: 2010 IEEE International Instrumentation and Measurement Technology Conference, I2MTC 2010 - Proceedings. pp. 691-696. doi:10.1109/IMTC.2010.5488085Ransom, D.L., 2013. Upgrading relay protection? Be prepared, in: 49th IEEE/IAS Industrial & Commercial Power Systems Technical Conference. IEEE, pp. 1-8. doi:10.1109/ICPS.2013.6547351Real-Calvo, R.J., Moreno-Munoz, A., Pallares-Lopez, V., Gonzalez-Redondo, M.J., Flores-Arias, J.M., 2014. Intelligent electronic device for the control of distributed generation, in: 2014 IEEE Fourth International Conference on Consumer Electronics Berlin (ICCE-Berlin). IEEE, pp. 268-269. doi:10.1109/ICCE-Berlin.2014.7034338Romero-Cadaval, E., Minambres-Marcos, V.M., Moreno-Munoz, A., RealCalvo, R.J., Gonzalez de la Rosa, J.J., Sierra-Fernandez, J.M., 2013. Active functions implementation in smart inverters for distributed energy resources, in: 2013 International Conference-Workshop Compatibility And Power Electronics. IEEE, pp. 52-57. doi:10.1109/CPE.2013.6601128Sharma, K., Mohan Saini, L., 2015. Performance analysis of smart metering for smart grid: An overview. Renew. Sustain. Energy Rev. 49, 720-735. doi:10.1016/j.rser.2015.04.170Su, W., Eichi, H., Zeng, W., Chow, M., 2012. A Survey on the Electrification of Transportation in a Smart Grid Environment. IEEE Trans. Ind. Informatics 8, 1-10. doi:10.1109/TII.2011.2172454Yalla, M.V.V.S., 1992. A digital multifunction protective relay. IEEE Trans. Power Deliv. 7, 193-201.Yan, Y., Qian, Y., Sharif, H., Tipper, D., 2013. A survey on smart grid communication infrastructures: Motivations, requirements and challenges. IEEE Commun. Surv. Tutorials 15, 5-20. doi:10.1109/SURV.2012.021312.0003