La caracterización del urbanismo de Le Corbusier: Los planes urbanos para las ciudades costeras

La obra urbanística de Le Corbusier se suele abordar desde de una mirada parcial propiciada por el análisis generalmente individualizado de sus propuestas. Es igualmente frecuente recurrir a su etapa inicial, caracterizada principalmente por su modelo para la Ville Contemporaine de 1922 o el Plan Voisin para París de 1925, y, por ende, sin atender a la amplia casuística derivada de casi tres décadas de actividad profesional. En este sentido, el presente artículo busca poner de manifiesto que la producción de Le Corbusier acumula una mayor amplitud conceptual. Para ello, se caracterizan cualitativa y cuantitativamente las propuestas urbanísticas que realizó para el conjunto de ciudades localizadas en áreas costeras, entendiendo que comparten características por su localización. La investigación considera los siguientes parámetros urbanísticos: demografía y densidad de población (1), la proporción de usos (2), la superficie edificada (3), la movilidad peatonal frente a la rodada (4) y la superficie de espacio público propuesto por número de habitantes (5). El análisis comparado entre el conjunto de planes urbanos de la muestra permite demostrar la diversidad y riqueza presente en el urbanismo de Le Corbusier, así como una notable evolución conceptual a lo largo de toda su trayectoria. Además de completar y ratificar aspectos intuidos desde acercamientos cualitativos previos. Se concluye abogando por superar la visión parcial que habitualmente caracteriza la crítica de su obra.publicad

Female upper reproductive tract harbors endogenous microbial profiles

The vaginal milieu is known to have an active microbiome (>90% of Lactobacillus), but the microbial composition of the upper reproductive tract is not well established, especially in the Fallopian tubes. The first studies on the Fallopian tubes from women diagnosed with a benign disease or for prophylaxis suggest that this site supports an endogenous microbiome. However, today we lack the knowledge of the microbial composition in Fallopian tubes in the non-diseased conditions (as collecting samples from these sites may hamper the tissue and future fertility). Our study includes 24 fertile women with benign uterine pathology submitted to abdominal hysterectomy or tubal ligation at Hospital Universitario Virgen de Arrixaca Murcia, which endometrial and Fallopian tube samples were collected between January and July 2019. After DNA extraction, “Ion 16S Metagenomics Kit” (Ion S5™ System) was used to exploit the V5 to V9 regions of the 16S rRNA gene. Primary data analysis was performed with Torrent Suite™ Software v5.12.1 and advanced analysis using Ion Reporter™ software v5.18.0.2. In our study, distinct microbial community profiles in the Fallopian tubes confirm that this genital tract site harbors an endogenous microbiome and in big part is shared with the endometrial microbial profile (69% of the detected taxa). Nevertheless, 17 bacterial taxa were exclusively detected in the Fallopian tubes that included Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes y Paracoccus, among others, while 10 were found only in the endometrium, including Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Regarding the endometrium samples, our study shows that method collection has an influence in results, where there is a Lactobacillus-dominance in fertile women with samples obtained transcervically while Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus, Streptococcus were less abundant in patients which samples are collected by methods with lower vaginal and cervical contamination. Although upper reproductive tract is a low microbial biomass site, our results suggest that this upper reproductive site supports an endogenous microbiome that could be characteristic of each individual

Synthesis of Catechol Derived Rosamine Dyes and Their Reactivity toward Biogenic Amines

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9−aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.Financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project PTDC/QUI-QOR/29426/2017. The research team would like to thank the projects UIDB/50006/2020, PTDC/QUI-QIN/28142/2017 and Grant BU263P18 (from the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo). F. M. -S. gratefully acknowledges FCT (Portugal’s Foundation for Science and Technology) within grant DFA/BD/9136/2020. A.M.G.S. and A.L. thank FCT for the program DL 57/2016 – Norma transitória

Matched cohort study on the efficacy of tocilizumab in patients with COVID-19

Background: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. Methods: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. Results: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: −0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). Conclusions: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge

Metodología para la creación y gestión de un sistema de seguimiento de egresados de la Facultad de Ciencias Matemáticas y su aplicación en la mejora de los títulos

Fac. de Ciencias MatemáticasFALSEUCMsubmitte

Reference Values to Assess Hemodilution and Warn of Potential False-Negative Minimal Residual Disease Results in Myeloma

This article belongs to the Special Issue Advances in Multiple Myeloma Research and Treatment.[Simple Summary] Although the majority of patients with myeloma who achieve undetectable minimal residual disease show prolonged survival, some of them relapse shortly afterwards. False-negative results due to hemodiluted bone marrow samples could explain this inconsistency, but there is no guidance on how to evaluate them. We analyzed three cell populations normally absent in peripheral blood in 1404 aspirates obtained in numerous disease settings and in 85 healthy adults. Pairwise comparisons according to age and treatment showed significant variability, thus suggesting that hemodilution should be preferably evaluated with references obtained after receiving identical regimens. Leveraging the minimal residual disease results from 118 patients, we showed that a comparison with age-matched healthy adults could also inform on potential hemodilution. Our study supports the routine assessment of bone marrow cellularity to evaluate hemodilution, using as reference values either treatment-specific or from healthy adults if the former are unavailable.[Abstract] Background: Whereas, in most patients with multiple myeloma (MM), achieving undetectable MRD anticipates a favorable outcome, some others relapse shortly afterwards. Although one obvious explanation for this inconsistency is the use of nonrepresentative marrow samples due to hemodilution, there is no guidance on how to evaluate this issue. Methods: Since B-cell precursors, mast cells and nucleated red blood cells are normally absent in peripheral blood, we analyzed them in 1404 bone marrow (BM) aspirates obtained in numerous disease settings and in 85 healthy adults (HA). Results: First, we confirmed the systematic detection of the three populations in HA, as well as the nonreduced numbers with aging. Pairwise comparisons between HA and MM patients grouped according to age and treatment showed significant variability, suggesting that hemodilution should be preferably evaluated with references obtained from patients treated with identical regimens. Leveraging the MRD results from 118 patients, we showed that a comparison with HA of similar age could also inform on potential hemodilution. Conclusions: Our study supports the routine assessment of BM cellularity to evaluate hemodilution, since reduced BM-specific cell types as compared to reference values (either treatment-specific or from HA if the former are unavailable) could indicate hemodilution and a false-negative MRD result.This study was supported by grants from the Centro de Investigación Biomédica en Red—Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400, CB16/12/00233 and CB16/12/00284); Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria and co-financed by FEDER funds (FIS No. PI15/01956, PI15/02049, PI15/02062, PI18/01709, PI18/01673 and PI19/01451); the Cancer Research UK (C355/A26819), FCAECC and AIRC under the Accelerator Award Programme (EDITOR); the Black Swan Research Initiative of the International Myeloma Foundation and the European Research Council (ERC) 2015 Starting Grant (Contract 680200 MYELOMANEXT). This study was supported by the Riney Family Multiple Myeloma Research Program Fund

Unravelling the Encapsulation of DNA and Other Biomolecules in HAp Microcalcifications of Human Breast Cancer Tissues by Raman Imaging

Microcalcifications are detected through mammography screening and, depending on their morphology and distribution (BI-RADS classification), they can be considered one of the first indicators of suspicious cancer lesions. However, the formation of hydroxyapatite (HAp) calcifications and their relationship with malignancy remains unknown. In this work, we report the most detailed three-dimensional biochemical analysis of breast cancer microcalcifications to date, combining 3D Raman spectroscopy imaging and advanced multivariate analysis in order to investigate in depth the molecular composition of HAp calcifications found in 26 breast cancer tissue biopsies. We demonstrate that DNA has been naturally adsorbed and encapsulated inside HAp microcalcifications. Furthermore, we also show the encapsulation of other relevant biomolecules in HAp calcifications, such as lipids, proteins, cytochrome C and polysaccharides. The demonstration of natural DNA biomineralization, particularly in the tumor microenvironment, represents an unprecedented advance in the field, as it can pave the way to understanding the role of HAp in malignant tissues

Inclusión de la harina de caña proteica en la alimentación de alevines de tilapia roja (Oreochromis spp.)

The biological effect of protein sugar cane meal inclusion in all isocaloric and isoprotein diets for red tilapia (Oreochromis spp.) alevins was evaluated. Four complete diets including 0 %, 10 %, 15 %, and 20 % of sugar cane meal protein were prepared. A total of 500 red tilapia alevins (Oreochromis spp.) weighing 1,55 ± 0,01 g were randomly distributed into 5 treatment reservoirs. Weight gain and food consumption were registered during 50 days to calculate daily weight gain, specific growth rate, food conversion rate, protein efficiency rate, and net protein utility. None of the inclusion levels showed significant differences compared to the control group. Findings support the inclusion of protein sugar cane meal in complete diets up to 20 % without affecting growth indexes, food supply and survival indicators.Se evaluó el efecto de la inclusión de harina de caña proteica en dietas isocalóricas e isoproteicas para alevines de tilapia roja (Oreochromis spp.) Se elaboraron cuatro dietas completas con 0; 10; 15 y 20 % de dicho alimento, elaborado a partir de caña de azúcar y ensilado de pescado. Un total de 500 alevines de 1,55 ± 0,01 g fueron distribuidos aleatoriamente en cinco piscinas por tratamiento. Durante 50 días se registró el crecimiento en peso y consumo de alimento para calcular el incremento de peso diario, tasa de crecimiento específico, factor de conversión alimentaria, tasa de eficiencia proteica y utilidad proteica neta. Ninguno de los niveles de inclusión mostró diferencias significativas con respecto al control; así, se concluye que la harina de caña proteica puede formar parte de dietas completas hasta en un 20 % de inclusión, sin que se afecten los indicadores de crecimiento, utilización de alimentos y supervivencia

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Background and aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. Approach and results: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. Conclusions: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.Funding information: Supported by grants from Ministerio de Ciencia, Innovación y Universidades MICINN (PID2020-117116RB-100, RTI2018-096759-A-100, RTI2018-095114-B-I00, PID2019-108977RB-100 and RTI2018-095700-B100, integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER, to M.L.M.-C., T.C.D., C.P., P.M.-S., and N.G.A.A., respectively), Subprograma Retos Colaboración RTC2019-007125-1; Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.); Asociación Española contra el Cáncer (to T.C.D. and M.S.-M); La Caixa Foundation Program (HR17-00601, to M.L.M.-C.), Proyectos Investigación en Salud DTS20/00138 (to M.L.M.-C.); Departamento de Industria del Gobierno Vasco (to M.L.M.-C.); Departamento de Educación del Gobierno Vasco (to N.G.-U. and J.S.); Acción Estratégica Ciber Emergentes 2018 (Ciberehd-ISCIII) and Gilead Sciences International Research Scholars Program in Liver Disease (to M.V.-R.); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos IIIAcknowledgments: We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). We acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided