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Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia Navas Jesús Hermosilla Anabel Torrente-lopez jose Hernandez-Jimenez jose Cabeza Raquel Perez-Roblesa Antonio Salmeron-garcía Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

Prevalence of meeting 24-Hour Movement Guidelines from pre-school to adolescence: A systematic review and meta-analysis including 387,437 participants and 23 countries

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Journal of Sport and Health Science 2022年第4期11卷 427-437页

作者： Miguel Angel Tapia-Serrano Javier Sevil-Serrano Pedro Antonio Sanchez-Miguel jose Francisco lopez-Gil Mark STremblay Antonio garcıa-Hermoso Department of Didactics of Musical Plastic and Body ExpressionFaculty of Teaching TrainingUniversity of ExtremaduraAvenida de la UniversidadS/NCaceres 10071Spain Department of Physical Activity and Sport Faculty of Sport ScienceUniversity of Murcia(UM)San Javier 30720Spain Healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario(CHEO)Research InstituteOttawaON K1H 8L1Canada Navarrabiomed Public University of Navarra(UPNA)Health Research Institute of Navarra(IdiSNA)Navarra Hospital Complex(CHN)Pamplona 310008Spaia

Background:Meeting the 24-Hour Movement Guidelines(physical activity,screen time,and sleep duration) has been associated with positive health indicators.However,there are no previous meta-analyses that have examined the overall adherence to the 24-Hour Movement Guidelines from pre-school to adolescence across the world.Therefore,the main purpose of this systematic review and meta-analysis was to examine the overall(non)adherence to the 24-Hour Movement Guidelines among preschoolers,children,and adolescents worldwide.Methods:Four electronic databases(MEDLINE,Scopus,Web of Science,and Cochrane Database of Systematic Reviews) were searched for quantitative studies published in Spanish and English between January 2016 and May 2021.Studies that were conducted with apparently healthy participants and reported the overall(non)adherence to the 24-Hour Movement Guidelines in preschoolers and/or children and/or adolescents were included.Results:Sixty-three studies comprising 387,437 individuals(51% girls) aged 3-18 years from 23 countries were included.Overall,7.12%(95%confidence interval(95%CI):6.45%-7.78%) of youth met all three 24-Hour Movement Guidelines,and 19.21%(95%CI:16.73%-21.69%)met none of the 3 recommendations.Concerning sex,adherence to all recommendations was significantly lower in girls(3.75%,95%CI:3.23%-4.27%) than in boys(6.89%,95%CI:5.89%-7.89%)(p <0.001).However,there were no sex differences regarding adherence to any of the 3 individual recommendations(girls,15.66%,95%CI:8.40%-22.92%;boys,12.95%,95%CI:6.57%-19.33%).In terms of age group,adherence to the 3 recommendations was 11.26%(95%CI:8.68%-13.84%),10.31%(95%CI:7.49%-13.12%),and 2.68%(95%CI:1.78%-3.58%) in preschoolers,children,and adolescents,respectively.Conversely,8.81%(95%CI:5.97%-11.64%) of preschoolers,15.57%(95%CI:11.60%-19.54%) of children,and 28.59%(95%CI:22.42%-34.75%) of adolescents did not meet any of the recommendations.South America was the region with the lowest adherence(all:2.93%;none:31.72%).Overall adherence to the 24-Hour Movement

关键词： Exercise Lifestyle Movement behaviors Sedentary behaviors Youth

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

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Regenerative Biomaterials 2019年第6期6卷 335-347页

作者： Filippo Cipriani Blanca Arino Palao Israel Gonzalez de Torre Aurelio Vega Castrillo Hector jose Aguado Hernandez Matilde Alonso Rodrigo Angel jose Alvarez Barcia Ana Sanchez Veronica garcıa Diaz Monica lopez Pena jose Carlos Rodriguez-Cabello Technical Proteins Nanobiotechnology S.L. Paseo Belen 9AValladolid 47011Spain Departamento de traumatologıa Hospital Clınico de ValladolidAv.Ramon y Cajal 3Valladolid 47003Spain Bioforge University of Valladolid CIBER-BBNPaseo de Belen 19Valladolid 47011Spain SIBA-UVA:servicio investigacion y bienestar animal University of ValladolidC/Plaza de Santa Cruz 8Valladolid 47002Spain Instituto de Biologıa y Genetica Molecular(IBGM) Universidad de Valladolid y CSICCalle Sanz y Fores 3Valladolid 47003Spain Facultad de veterinaria Campus UniversitarioAvda.Carballo Calero s/nLugo 27002Spain

The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral repair.Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits.Thus,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the defects.Although both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage.In conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

关键词： biopolymer animal test cartilage bone

Land-use change and windstorms legacies drove the recolonization dynamics of laurel forests in Tenerife, Canary islands

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Forest Ecosystems 2023年第1期10卷 113-124页

作者： Vicente Rozas Maria A.garcia-lopez jose M.Olano Gabriel Sanguesa-Barreda Miguel garcia-Hidalgo Susana Gomez-Gonzalez Roberto lopez-Rubio jose M.Fernandez-Palacios Ignacio garcia-Gonzalez Laura Lozano-lopez Paula garcia-Gonzalez Ana I.garcia-Cervigon EiFAB-iuFOR Universidad de ValladolidCampus Duques de Soria42004SoriaSpain Departamento de Biologia-IVAGRO Universidad de CadizCampus Rio San Pedro11510Puerto RealSpain Center for Climate and Resilience Research(CR)2 Blanco Encalada 20028370449SantiagoChile Area de Biodiversidad y Conservacion Universidad Rey Juan Carlosc/Tulipan s/n28933MostolesSpain Grupo de Ecologia y Biogeografia Insular Universidad de La Laguna38206La LagunaTenerifeSpain BIOAPLIC Departamento de BotanicaEscola Politecnica Superior de EnxenariaCampus TerraUniversidade de Santiago de CompostelaLugo27002Spain

Laurel forests are quite relevant for biodiversity conservation and are among the island ecosystems most severely damaged by human activities.In the past,Canary laurel forests have been greatly altered by logging,livestock and agriculture.The remains of laurel forests are currently protected in the Canary Islands(Spain).However,we miss basic information needed for their restoration and adaptive management,such as tree longevity,growth potential and responsiveness to natural and anthropogenic disturbances.Using dendrochronological methods,we studied how forest dynamic is related to land-use change and windstorms in two well-preserved laurel forests on Tenerife Island.Wood cores were collected from over 80 trees per stand at three stands per forest.We used ring-width series to estimate tree ages and calculate annual basal area increments(BAI),cumulative diameter increases,and changes indicative of released and suppressed growth.Twelve tree species were found in all stands,with Laurus novocanariensis,Ilex canariensis and Morella faya being the most common species.Although some individuals were over 100 years old,61.8%-88.9% of the trees per stand established between 1940 and 1970,coinciding with a post-war period of land abandonment,rural exodus and the onset of a tourism economy.Some trees have shown growth rates larger than 1 cm diameter per year and most species have had increasing BAI trends over the past decades.Strong growth releases occurred after windstorms at both sites,but the effects of windstorms were site-dependent,with the 1958 storm affecting mainly the eastern tip of the island(Anaga massif)and the 1991 storm the western tip(Teno massif).Given the great ability of laurel forest trees to establish after land use cessation and to increase growth after local disturbances such as windstorms,passive restoration may be sufficient to regenerate this habitat in currently degraded areas.

关键词： Canary islands Dendroecology Disturbance Forest structure Macaronesia Management cessation Tree rings

Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases

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Neural Regeneration Research 2020年第8期15卷 1408-1416页

作者： jose A.Fernandez-Albarral Rosa de Hoz Ana I.Ramirez Ines lopez-Cuenca Elena Salobrar-garcia Maria D.Pinazo-Duran jose M.Ramirez Juan J.Salazar Instituto de Investigaciones Oftalmologicas Ramon Castroviejo MadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de Optica y OptometriaMadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de MedicinaMadridSpain Unidad de Investigacion Oftalmologica Santiago Grisolia Universidad de ValenciaValenciaSpain

Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

关键词： AMD crocetin crocin Crocus sativus L. diabetic retinopathy glaucoma neuroprotection ocular diseases retinitis pigmentosa saffron safranal

A Pilot Test for A One-year Cognitive Training Intervention in Elderly Adults with Mild Cognitive Impairment

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Biomedical and Environmental Sciences 2020年第10期33卷 796-802页

作者： MENDOZA-HOLGADO Cristina lopez-ESPUELA Fidel MORAN jose Maria RONCERO-MARTIN Raul LAVADO-garcIA Jesus ALIAGA Ignacio PUERTO-PAREJO Luis Manuel LEAL-HERNANDEZ Olga VERA Vicente PEDRERA-CANAL Maria Nursing Department Metabolic Bone Disease Research GroupUniversity of ExtremaduraNursing and Occupational Therapy CollegueAvd.Universidad s/n10003-CaceresSpain Facultad de Odontologia Universidad ComplutenseMadridSpain

In Spain,the proportion of elderly individuals has increased to 19.1%.By 2068,the proportion of elderly individuals is estimated to increase to 29.4% given the largest birth cohorts in Spain’s history(Instituto Nacional de Estadistica,INE).This challenge needs a supportive plan,as economic and caring problems may occur because of age-related health problems,including cognitive decline and dementia[1].

关键词： elderly Pilot Training

High-resolution patterns of palaeoenvironmental changes during the Little Ice Age and the Medieval Climate Anomaly in the northwestern Iberian Peninsula

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Geoscience Frontiers 2020年第5期11卷 1461-1475页

作者： Daniel Castro Martin Souto Maria Isabel Fraga Eduardo garcia-Rodeja Sebastian Perez-Diaz jose Antonio lopez Saez Xabier Pontevedra-Pombal Dpto.Botanica Fac.BioloxiaUniversidade de Santiago de CompostelaGaliciaSpain Dpto.Edafoloxia e Quimica Agricola Fac.BioloxiaUniversidade de Santiago de CompostelaGaliciaSpain Dpto.Geografia Urbanismo y Ordenacion Del TerritorioETS CaminosCanales y PuertosUniversidad de CantabriaSpain GI Arqueobiologia Instituto de HistoriaCCHS–CSICMadridSpain

to identify plant macrofossils,estimate peat humification and calculate hydroclimatic indices based on current bog species,with the overall aim of determining the climate conditions associated with evolution of the bog during the Medieval Climate Anomaly and the Little Ice Age.These proxies,together with historical and climate data,proved to be good indicators of the changes in bog surface wetness.Analysis:of the core led to identification of 9 different periods:two corresponding to the so-called Medieval Climate Anomaly(930 to 1345 AD,1075–665 calibrated years before present[cal.yr BP]);four corresponding to the Little Ice Age(1345 to 1905 AD;665–105 cal yr BP);and three corresponding to the last century(1905 to 2000 AD).The findings revealed a generally dry climate that lasted until the 14th century,followed by a transition to a long period with a more humid,but characteristically very variable climate,which ended at the beginning of the 20th century and was followed by a rapid transition to more humid conditions and finally,a change to drier conditions.The Medieval Climate Anomaly was indicated by the abundance of dry-adapted mosses(Leucobryum glaucum,Hypnum cupressiforme)and characterized by warm dry conditions and high levels of peat humification,with alternating wet phases.The LIA period was dated by a large abundance of Sphagnum species(an indicator of wetness)and a gradual increase in the humification index.However,four different climate phases were differentiated in this period.High-resolution reconstruction of the evolution of the CVM bog and the multiproxy approach have together enabled a more detailed identification of climatic variations in this area,which are generally consistent with the global models,as well as better definition of the elusive climatic oscillations in the last millennium and confirmation of the importance of local modulation of global models.The study provides new information and a detailed chronology of climatic events that will help to refine local modulation of the climate evol

关键词： Last millennium Raised bog Plant macrofossil Humification analysis Southwest Europe Climate change

Nonlinear parabolic predator-prey coupled system with convection

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International Journal of Biomathematics 2021年第2期14卷 83-118页

作者： jose Luis Diaz Palencia Mariano Fernandez lopez University Foundation San Pablo CEU Spain

The aim of this work is to provide a formulation of two related nonlinear diffusive convective models in the form of coupled reaction-absorption equations.First,the postulated models are studied with an analytical approach.Later on,numerical evidences are considered to account for a precise characterization.The problem(P)analyzed is of the form:ut=δΔu+c⋅∇u+v^(n),vt=ϵΔv+c⋅∇v−um,n,m∈(0,1),u_(0)(x),v_(0)(x)>0∈L^(1)_(loc)(RN)∩L^(∞)(R^(N)).(0.1)Afterwards,a related problem P_(T)is studied:ut=δΔu+c⋅∇u−v^(n)(u−d),vt=ϵΔv+c⋅∇v−u^(m)v,n,m∈(0,1),u_(0)(x),v_(0)(x)>0∈L^(1)_(loc)(R^(N))∩L^(∞)(R^(N)).(0.2)The principal aspects for analysis are related to the existence and the derivation of particular solutions to reproduce the dynamic of the interacting species.For the problem PT,we make use of the TW approach to study existence of solutions and precise evolution of profiles.Note that the term predator is used to refer to an invasive behavior,while the term prey is used for the invaded species.

关键词： Nonlinearity reaction absorption coupled system diffusion,traveling waves

Female mate choice based on pheromone content may inhibit reproductive isolation between distinct populations of Iberian wall lizards

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Current Zoology 2013年第2期59卷 210-220页

作者： Marianne GABIROT Pilar lopez jose MARTIN Departement Ecologie Comportementale (U.M.R. 5175) CEFE-CNRS 1919 Route de Mende F34293 Montpellier Cedex 5 France Departamento de Ecologia Evolutiva Museo Naeional de Ciencias Naturales C.S.I.C. Jos6 Guti6rrez Abascal 2 28006 Madrid Spain

The Iberian wall lizard Podarcis hispanica forms part of a species complex with several morphologically and geneti- cally distinct types and populations, which may or may not be reproductively isolated. We analyzed whether female mate choice based on males' chemical signals may contribute to a current pre-mating reproductive isolation between two distinct populations of P. hispanica from central Spain. We experimentally examined whether females choose to establish territories on areas scent-marked by males of their own population, versus areas marked by males of the other population. Results showed that fe- males did not prefer scent-marks of males from their own population. In contrast, females seemed to attend mostly to among-individual variation in males' pheromones that did not differ between populations. Finally, to test for strong premating re- productive isolation, we staged intersexual encounters between males and females. The population of origin of males and females did not affect the probability nor the duration of copulations. We suggest that the different environmental conditions in each population might be selecting for different morphologies and different chemical signals of males that maximize efficiency of communication in each environment. However, females in both populations based mate choice on a similar condition-dependent signal of males. Thus, male signals and female mate choice criteria could be precluding premating reproductive isolation between these phenotypically "distinct" populations [Current Zoology 59 (2): 210-220, 2013].

关键词：生殖隔离女性择偶人群蜥蜴信息素化学信号气味标记