Value of Early Circulating Tumor Cells Dynamics to Estimate Docetaxel Benefit in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients

Biomarcadores; Células tumorales circulantes; DocetaxelBiomarkers; Circulating tumor cells; DocetaxelBiomarcadors; Cèl·lules tumorals circulants; DocetaxelCirculating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3–6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3–6 weeks (CTC conversion (from ≥5 to <5 CTCs), CTC30 (≥30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.The results reported here were generated as part of two academic studies supported by various grants. The funding sources had no role in study design, data analysis, data interpretation or writing of the report. R.L., D.L. and D.O. had full access to all of the data and had final responsibility for the decision to submit for publication. This project represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

What knowledge and conceptions mobilize future teachers analyzing a classroom video?

El uso del vídeo de sesiones de clase de Educación Primaria (EP) en la formación inicial del maestro aporta realismo a las discusiones teóricas de las aulas de magisterio, contribuyendo a la vinculación entre la teoría y la práctica sobre la base de procesos reflexivos que ayudan a trascender los habituales comentarios genéricos de los estudiantes para maestro (EPM). El objetivo de este estudio es identificar las concepciones sobre la enseñanza y el aprendizaje de las matemáticas así como el conocimiento matemático para la enseñanza (particularmente el conocimiento de matemáticas y la enseñanza y el conocimiento de matemáticas y los estudiantes) que un grupo de EPM pone en juego cuando observa un vídeo de EP. Mediante un diseño de investigación consistente con un experimento de enseñanza (Steffe y Thompson, 2000) (en el que un diseño instruccional, orientado a los EPM, acerca de la introducción del concepto de división, se va refinando a través de sucesivos ciclos de implementación y análisis), se pone de relieve cómo el análisis de situaciones de enseñanza en EP promueve el cuestionamiento de los EPM.The use of the Primary Education (PE) class sessions video in the initial training of teachers provides realism to the theoretical discussions of Master’s degree classrooms, contributing to the link between theory and practice on the basis of reflective processes that help to transcend the normal general comments of teacher students (TS). The objective of this study is to identify the conceptions for the teaching and learning of mathematics, as well as the mathematical knowledge for teaching (particularly the knowledge of mathematics and the teaching and knowledge of mathematics and students) that a group of TS use when observing a PE video. Using a research design consistent with a teaching experiment (Steffe and Thompson, 2000) (in which an instructional design, aimed at TS, regarding the introduction of the concept of division, is refined by means of successive cycles of implementation and analysis), the way the analysis of teaching situations in PE promotes the questioning of TS is highlighted.O uso de vídeos de sessões de aula de Educação Primária (EP) na formação inicial do professor oferece realismo às discussões teóricas sobre as aulas de magistério, contribuindo para a vinculação entre a teoria e a prática sobre a base de processos reflexivos que ajudam a transcender os habituais comentários genéricos dos estudantes para professores (EPM). O objetivo deste estudo é identificar as concepções sobre o ensino e a aprendizagem da matemática, assim como o conhecimento matemático para o ensino (particularmente o conhecimento de matemática e o ensino e o conhecimento de matemática e dos estudantes) que um grupo de EPM põe em jogo quando observa a um vídeo de EP. Através de uma criação de pesquisa consistente com um experimento de ensino (Steffe e Thompson, 2000), destaca-se como a análise de situações de ensino em EP promove o questionamento dos EPM.L’utilisation de la vidéo pour une classe d’élèves en école primaire (EP) durant la formation des futurs instituteurs confère un certain réalisme aux discussions théoriques qui ont lieu dans les cours de formation des instituteurs (l’équivalent en France des IUFM) en contribuant à la création de liens entre théorie et pratique basés sur des processus réflexifs qui permettent aux étudiants d’aller au-delà des habituels commentaires généraux. L’objectif de la présente étude consiste à identifier les conceptions sur l’enseignement et l’apprentissage des mathématiques ainsi qu’à s’interroger sur la connaissance mathématique pour l’enseignement (en particulier, la connaissance des mathématiques et l’enseignement des mathématiques et les étudiants) qu’un groupe de futurs instituteurs utilise lorsqu’il observe une vidéo conçue pour l’école primaire. Grâce à un travail de recherche qui va de pair avec une expérience sur l’enseignement (Steffe et Thompson, 2000) (dans lequel un travail propre à l’enseignement conçu pour les futurs instituteurs portant sur l’introduction du concept de division s’affine de plus en plus au fur et à mesure que des cycles successifs de mises en oeuvre et d’analyse sont utilisés), on montre comment l’analyse de situations en école primaire suscite le questionnement des futurs instituteurs

Shear-induced microstructural transitions in aqueous systems containing an esterquat cationic surfactant

Se presenta un estudio basado en técnicas reológicas y de microscopía electrónica de barrido de bajas temperaturas (cryo-SEM) sobre los cambios de microestructura provocados por el flujo en cizalla de dispersiones acuosas de un tensioactivo catiónico tipo esterquat. Se comparan micrografías de cryo-SEM y las respuestas bajo cizalla oscilatoria de dispersiones sin y con cloruro de calcio. Esta última no presenta zona de comportamiento viscoelástico lineal, apuntando su respuesta no lineal a un fenómeno de estructuración inducida por cizalla. Ensayos transitorios de inicio al flujo, entre 0,1s-1 y 2000s-1, confirman que se producen aumentos de viscosidad más acusados con el tiempo de flujo a medida que aumenta la velocidad de cizalla. La técnica de cryo-SEM apoya que los resultados transitorios se deben a que un exceso de energía mecánica provoca transiciones de bicapas de tensioactivo a vesículas. Diferentes ensayos reológicos realizados en serie avalan la naturaleza irreversible, en la escala de tiempo de esta investigación, de las transiciones microestructurales inducidas por cizalla. Se demuestra que a pesar de la presencia de cloruro de calcio (0,1%), la aplicación de una velocidad de cizalla excesiva puede dar lugar a la aparición de respuestas viscoelásticas lineales significativas.This paper deals with a rheological and microstructural (cryo- SEM) characterization of shear-induced microstructure transitions in aqueous dispersions of an esterquat cationic surfactant. Cryo-SEM micrographs and oscillatory shear results of systems containing or not calcium chloride are compared. The addition of calcium chloride precluded the occurrence of significant viscoelastic properties and the estimation of the linear viscoelastic range. The non-linear oscillatory response pointed to the occurrence of incipient shear-induced build-up phenomena. Start-up flow tests between 0.1s-1 and 2000s-1 showed that the increase of viscosity with shear time was more marked as shear rate was increased. Cryo-SEM observations supported that build-up results in transient flow were due to an excess of mechanical energy, which resulted in transitions from surfactant bilayers to vesicles. Several series of rheological tests were carried out to demonstrate that shear-induced microstructure transitions were irreversible in the time scale of this investigation. Despite the addition of calcium chloride (0.1% wt), the shear-induced dispersion of vesicles may provoke the onset of significant linear viscoelasticity.Es presenta un estudi basat en tècniques reològiques i de microscòpia electrònica d’escombratge de baixes temperaturas (cryo-SEM) sobre els canvis de microestructura provocats pel flux en cisalla de dispersions aquoses d’un tensioactiu catiònic tipus esterquat. Es comparen micrografies de cryo-SEM i les respostes sota cisallament oscil•latòri de dispersions sense i amb clorur de calci. Aquesta darrera no presenta zona de comportament viscoelàstic lineal, apuntant la seva resposta no lineal a un fenomen d’estructuració induïda per cisallament. Assaigs transitoris d’inici al flux, entre 0,1s-1 y 2000s-1, confirmen que es produeixen augments de viscositat més acusats amb el temps de flux a mesura que augmenta la velocitat de cisallament. La técnica de cryo-SEM recolza que els resultats transitoris es deuen a que un excés d’energia mecànica provoca transicions de bicapes de tensioactiu a vesícules. Diferents assaigs reològics realitzats en sèrie avalen la naturalesa irreversible, a la escala de temps d’aquesta investigació, de les transicions microestructurals induïdes per cisallament. Es demostra que, tot i la presència de clorur de calci (0,1%), l’aplicació de una velocitat de cisallament excessiva pot donar lloc a l’aparició de respostes viscoelàstiques lineals significatives

Injectable hydrogels based on pluronic/water systems filled with alginate microparticles: Rheological characterization

In this paper the rheological characterization of Pluronic/water systems filled with alginate microparticles is presented. The rheological characterization of the Pluronic/water systems allowed for the choice of the best Pluronic concentration taking into account its applications as injectable hydrogels for tissue repair. The effect on the rheological behavior of the addition of alginate microparticles, to be loaded with the drug, was analyzed and the maximum concentration of microparticles determined.Spanish Ministerio de Economia y CompetitividadV Plan Propio Universidad de SevillaEuropean Union (EU)Portuguese Foundation for Science and Technology 288 UID/CTM/50025/201

Influence of different surgical techniques on primary implant stability in the posterior maxilla: a randomized controlled clinical trial

Background and objective Primary stability (PS) is remarkable for secondary stability and implant success. Surgical technique modifications seem to improve primary stability, especially in poor quality bone. The aim of this study was to compare the insertion torque (IT) and implant stability quotients (ISQ) of implants placed with underpreparation, expanders, and standard surgical instrumentation in different bone types. Material and methods This randomized controlled clinical trial enrolled 108 patients (n=108 implants) distributed in three study groups: group 1 (n=36) underpreparation technique, group 2 (n=36) expander technique, and group 3 (n=36) conventional drilling. IT was recorded with a torque indicator. ISQ was recorded with resonance frequency analysis immediately after surgery. Results ISQ values were associated with the patient’s bone quality and were higher in bone quality type II (76.65) and type III (73.60) and lower in bone quality type IV (67.34), with statistically significant differences (p<0.0001). Lower stability results were obtained when conventional drilling (69.31) was used compared to the use of underpreparation (74.29) or expanders (73.99) with a level of significance of p=0.008 and p=0.005, respectively. Conclusions The surgical technique influences the PS when there is low-quality bone. In low-quality bones, conventional drilling obtains lower ISQ values. Clinical relevance Replace the conventional drilling technique for an alternative, underpreparation or expanders, in lowquality bone in order to achieve greater primary stabilityUniversidad de Granada/ CBU

Zonda is a novel early component of the autophagy pathway in Drosophila

Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions, and soon after starvation nucleates in endoplasmic reticulum-associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13 and Atg17 but does not require Vps34, Vps15, Atg6 or Atg14. Zonda interacts physically with ATG1 through its kinase domain, as well as with ATG6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation

Methodology for development of ecological emulsions formulated with green solvents or essential oils

Las emulsiones ecológicas se formulan y preparan idealmente siguiendo los principios del desarrollo sostenible o la química verde. Estas emulsiones verdes poseen un gran número de aplicaciones, ya que por ejemplo son utilizadas en la industria alimentaria. La industria química está mostrando especial atención a la sustitución de los disolventes sintéticos por disolventes ecológicos en el desarrollo de emulsiones aceite-en-agua para usos agroquímicos, como pinturas, tintas de impresión, desengrasantes y como limpiadores. Los disolventes ecológicos se utilizan cada vez más como consecuencia de la prohibición de algunos disolventes orgánicos tradicionales y sintéticos. Por este motivo, los científicos e ingenieros responsables del desarrollo de productos están afrontando el desafío de formular emulsiones que contienen nuevos disolventes, tensioactivos o aditivos obtenidos a partir de fuentes renovables y con buenas propiedades ecológicas. En este capítulo se desarrolla una metodología para el desarrollo de emulsiones ecológicas con componentes obtenidos a partir de fuentes renovables, de nula toxicidad y biodegradables como una alternativa sostenible a aquellos productos que contienen disolventes orgánicos tradicionales.Green emulsions are formulated and ideally prepared under the principles of the so-called sustainable development or green chemistry and find a great variety of applications. These systems are increasingly used by the food industry insofar as there is an increasing tendency to reduce the number of synthetic additives and to increase the use of biomaterials and ingredients with functional properties. For similar reasons they are more and more used by the pharmaceutical and cosmetic industries. The chemical industry is also paying attention to the substitution of synthetic solvents by green solvents in water-based emulsions used as agrochemicals, paints, printing inks, fat removers and all-purpose cleaners. Green solvents are increasingly used since many synthetic solvents have been banned due to their carcinogenic or toxic properties and to their poor biodegradability. For this reason, scientists and engineers responsible for product development face the challenge to formulate emulsions containing new solvents, surfactants and additives obtained from renewable raw materials and exhibiting enhanced ecological properties.Plan Propio de la Universidad de Sevilla Proyecto: 2017/00000962Ministerio de Economía y Competitividad (España) / FEDER, UE CTQ2011-27371Ministerio de Economía y Competitividad (España) / FEDER, UE CTQ2015-7070

Estudio de la estabilidad física, propiedades reológicas y microestructura de sistemas Aerosil 200/agua. Influencia de un tensioactivo no iónico

Se han estudiado las propiedades reológicas, la estabilidad física y la microestructura de suspensiones de una sílice hidrofílica (Aerosil 200) en agua con potencial aplicación como fase continua de emulsiones ecológicas. Además, se analizó la influencia de la adición de Amidet N, un tensioactivo no iónico derivado del aceite de Colza, en las propiedades viscoelásticas y la microestructura de las dispersiones. Se muestran diferentes comportamientos reológicos dependiendo de la concentración de Aerosil 200 en los sistemas binarios. Existe un aumento importante del carácter gel del 8% al 9% de Aerosil 200 mejorando la estabilidad física. Este cambio está relacionado con el grado de interacción de las partículas, como se muestra en la microscopia electrónica de barrido (Cryo-SEM). La adición de Amidet N a la suspensión provocó un incremento de los módulos viscosos y elásticos mostrándose una estructura más compacta. El sistema que contiene 6% de Aerosil 200 y 3% de Amidet N mostró adecuadas propiedades reológicas para su uso como fase continua de emulsiones que respetan el medio ambiente. Finalmente, cabe destacar el interés del estudio de este tipo de sistemas intermedios como punto de partida para el desarrollo de emulsiones.Aerosil 200/water dispersions and Aerosil 200/water/Amidet N were studied by means of rheological, microstructural and multiple light scattering techniques. These systems can find application as continuous phase in emulsions. Rheological tests such as flow curve and small amplitude oscillatory shear tests detected an abrupt change of behaviour related to microstructural interaction grade reflected through the Cryo-SEM micrographs. The most concentrated systems turned out to be more physically stable. An increase of viscoelastic properties was detected as a consequence of addition of Amilet N, which led to more compact microstructure. Finally, it is worth noting the interest of studying this type of intermediate systems as a starting point for the development of emulsions.Plan Propio de la Universidad de Sevilla Proyecto: 2017/00000962Ministerio de Economía y Competitividad (España) / FEDER, UE CTQ2015-70700-

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic

Candida parapsilosis; Antifungal resistance; OutbreaksCandida parapsilosis; Resistencia antifúngica; BrotesCandida parapsilosis; Resistència antifúngica; BrotsBackground Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020–2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.O.Z. was funded by grants SAF2017–86912-R and PID2020–114546RB-I00 from the Spanish Ministry for Science and Innovation. This work was also funded by the National Centre for Microbiology (Instituto de Salud Carlos III) through the Surveillance Program of Antifungal Resistance and the Center for Biomedical Research in Network of Infectious Diseases CIBERINFECTCB21/13/00105 (O.Z. and L.A.F.), CIBERINFEC-CB21/13/00009 (M.P.-A.), CIBERES-CB06/06/0037 (C.A.-T.), and CIBERES-CB06/06/0058 (J.G). L.A.-F. was supported by Fondo de Investigación Sanitaria (MPY 117/18 and MPY 305/20). We thank Dr. David Campany Herrero (Vall d’Hebron Hospital), Noelia Garrido Peño (Móstoles Hospital), David Gómez Gómez y Aitziber Illaro Uranga (Marqués de Valdecilla Hospital), María Ángeles Machín Morón (Burgos Hospital), Jose Manuel Caro Teller (Doce de Octubre Hospital), Marina Calvo (Puerta de Hierro Hospital), and Ariadna Padulles (Bellvitge Hospital) for providing the data on antifungal consumption from their hospitals. We also thank Ángel Zaballos and Pilar Jiménez from the Genomics Core Facility from Instituto de Salud Carlos III for their technical help with the microsatellite analysis technique

Imported strongyloidiasis: Data from 1245 cases registered in the +REDIVI Spanish Collaborative Network (2009-2017)

Strongyloidiasis; Spain; Collaborative NetworkEstrongiloïdosi; Espanya; Xarxa Col·laborativaEstrongiloidosis; España; Red ColaborativaBACKGROUND: Imported strongyloidiasis is increasingly being diagnosed in non-endemic areas. The aim of this study was to describe the epidemiological, clinical and microbiological characteristics of patients with imported strongyloidiasis in Spain. METHODOLOGY: This is an observational retrospective study that included all patients diagnosed of strongyloidiasis registered in the +REDIVI Collaborative Network from 2009 to 2017. Demographic, epidemiological and clinical information was collected from the +REDIVI database, and extra information regarding microbiological techniques, treatment and follow-up was requested to participant centers. FINDINGS: Overall, 1245 cases were included. Most of them were immigrants (66.9%), and South America was the most frequent area of origin. Detection of larvae in stool samples was observed in 21.9% of the patients, and serological tests allowed making the diagnosis in the rest of the cases. Eosinophilia was present in 82.2% of cases. Treatment with ivermectin (compared with albendazole) was the most strongly associated factor to achieve the cure (OR 2.34). CONCLUSIONS: Given the long latency of the infection and the risk of developing a severe presentation, screening of S. stercoralis infection should be mandatory in patients coming from or had traveling to endemic areas, especially in those with immunosuppressant conditions