Phonological fluency norms for Spanish middle-aged and older adults provided by the SCAND initiative (P, M, & R)

Objective: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. Method: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). Results: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. Conclusions: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessmentObjective: Verbal fluency tests are quick and easy to administer neuropsychological measures and are regularly used in neuropsychological assessment. Additionally, phonological fluency is a widely used paradigm that is sensitive to cognitive impairment. This paper offers normative data of phonological verbal fluency (letters P, M, R) for Spanish middle- and older-aged adults, considering sociodemographic factors, and different measures such as the total number of words, errors (perseveration and intrusions), and 15 sec-segmented scores. Method: A total of 1165 cognitively unimpaired participants aged between 50 and 89 years old, participated in the study. Data for P were obtained for all participants. Letters M and R were also administered to a subsample of participants (852) aged 60 to 89 years. In addition, errors and words produced every 15 seconds were collected in the subsample. To verify the effect of sociodemographic variables, linear regression was used. Adjustments were calculated for variables that explained at least 5% of the variance (R2 ≥ .05). Results: Means and standard deviations by age, scaled scores, and percentiles for all tests across different measures are shown. No determination coefficients equal to or greater than .05 were found for sex or age. The need to establish adjustments for the educational level was only found in some of the measures. Conclusions: The current norms provide clinically useful data to evaluate Spanish-speaking natives from Spain aged from 50 to 89 years. Specific patterns of cognitive impairment can be analyzed using these normative data and may be important in neuropsychological assessmentS

Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease

Background Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease. In addition, the beneficial effects of coenzyme Q10 (CoQ) supplementation on cellular alterations were evaluated. Chemically-induced Gaucher macrophages were developed by differentiateing THP-1 monocytes to macrophages by treatment with phorbol 12-myristate 13-acetate (PMA) and then inhibiting intracellular GCase with conduritol B-epoxide (CBE), a specific irreversible inhibitor of GCase activity, and supplementing the medium with exogenous GlcCer. This cell model accumulated up to 16-fold more GlcCer compared with control THP-1 cells. Results Chemically-induced Gaucher macrophages showed impaired autophagy flux associated with mitochondrial dysfunction and increased oxidative stress, inflammasome activation and impaired efferocytosis. All abnormalities were partially restored by supplementation with CoQ. Conclusion These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD.info:eu-repo/semantics/publishedVersio

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na(+)/Ca(2+) exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na(+)/K(+) pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis.This work was supported by FIS PI10/00543 grant, FIS EC08/00076 grant, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, and by AEPMI (Asociación de Enfermos de Patología Mitocondrial).Peer reviewe

ErbBs inhibition by lapatinib blocks tumor growth in an orthotopic model of human testicular germ cell tumor

In this work, we have analyzed the expression of different members of the ErbB family in human samples of testicular germ cell tumors (GCTs). We observed expression of ErbB1 or ErbB2 in different tumor subtypes, but we also found high expression of ErbB3 in all GCTs tested. This pattern of expression was maintained when primary tumors were orthotopically implanted in nude mice. We have chosen a choriocarcinoma model characterized by high levels of ErbB1, but also of ErbB2 and ErbB3, to assay the in vivo effect of ErbB inhibitors on tumoral growth. Our results showed a complete lack of effect (refractoriness) to the pure ErbB1 receptor inhibitors cetuximab and gefitinib. While these inhibitors blocked ErbB1 phosphorylation, ErbB2 phosphorylation was not affected, suggesting an ErbB1-independent activation of this receptor. To confirm the importance of ErbB2 activation, animals were treated with lapatinib, a dual ErbB1 and ErbB2 inhibitor. Lapatinib treatment caused a 50% inhibition in tumor growth, an effect correlated with a blockade of both ErbB1 and ErbB2 phosphorylation levels, and of downstream signaling pathways (Akt, ERKs and Stat3). ErbB2 activation could still occur due to the formation of ErbB2/ErbB3 heterodimers, and ErbB3 activation was completely inhibited by lapatinib. Finally, combined inhibition of ErbB1 (gefitinib) and ErbB3 activities (knockdown expression by shRNA) inhibited tumoral testicular cells proliferation in a similar way to lapatinib. Our results explain why lapatinib but not anti-ErbB1 agents might be effective for treatment of testicular GCT patients

Quatro ou Mais Pontos de Vista sobre o Ensino de Análise Matemática

Resumo Neste artigo apresentamos resultados de pesquisas focados na disciplina de análise, no âmbito de cursos de licenciatura em matemática, tendo como pano de fundo um panorama de como a disciplina vem se estruturando, no cenário brasileiro, no que diz respeito aos seus objetivos, conteúdos e bibliografia. Num primeiro momento vimos, de forma sucinta, como coordenadores de cursos e professores da disciplina compreendem o papel da análise na licenciatura. Num segundo momento, e constituindo o objetivo principal do trabalho, apresentamos o que pensam licenciandos e professores de matemática da educação básica a respeito dessa disciplina, por meio de uma pesquisa qualitativa inspirada em uma postura fenomenológica. Após os procedimentos metodológicos, chegou-se a três categorias abertas: “A presença da análise na licenciatura em matemática”, “A análise como corpo de conhecimento” e “A análise e a abertura de horizonte de possibilidades do professor”, que foram interpretadas com o intuito de transcender as manifestações de cada indivíduo, em um movimento de síntese compreensiva. Finalmente, num terceiro momento, apresentamos algumas propostas em andamento e perspectivas futuras para os trabalhos sobre ensino de análise

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

EFECTO DE AUXINAS Y CITOQUININAS EN EL CULTIVO DE TEJIDO DE AHNFELTIA PLICATA (HUDSON) FRIES, 1836 (AHNFELTIALES, RHODOPHYTA) DE LA REGIÓN DE MAGALLANES

Ahnfeltia plicata (Hudson) Fries, 1836, es una agarófita comercialmente importante, que ocurre en la Región de Magallanes y caracterizada por presentar un ciclo de vida heteromórfico. Se han utilizado técnicas de cultivo in vitro para la micropropagación de diferentes especies de microalgas, sin embargo, no hay antecedentes del uso de estas tecnologías con A. plicata. El objetivo de este estudio fue desarrollar técnicas de cultivo in vitro de tejido vegetativo de A. plicata para micropropagación utilizando 2 reguladores de crecimiento de plantas superiores: 6-Bencilaminopurina (BAP) y ácido Indolacético (IAA) bajo diferentes condiciones de cultivo. Fueron utilizados talos gametofíticos no reproductivos de regiones apicales y porciones medias, de los cuales se obtuvieron explantes de 5 mm. Los reguladores de crecimiento de plantas superiores fueron utilizados en 3 concentraciones: 0.1 mg/L, 1.0 mg/L y 5.0 mg/L, preparadas en medio de cultivo Provasoli. El experimento se realizó en triplicado para cada concentración de estos reguladores de crecimiento y para cada sección del talo, utilizando un n= 4 explantes por placa de cultivo en dos fotoperiodos (16:8 y 12:12, luz: oscuridad), a una temperatura de 10°C e intensidad luminosa de 9 - 10 μmol seg-1 m-2. Se realizaron monitoreos y mediciones de cada explante cada siete días. Se observó que ambos reguladores de crecimiento de plantas superiores promueven el crecimiento de Ahnfeltia plicata. El medio de cultivo enriquecido con IAA estimuló el crecimiento en regiones polares de los explantes de A. plicata, mientras que al utilizar BAP se observó crecimiento tanto en regiones polares como formación de ramificaciones laterales. El proceso de regeneración de explantes mostró mejor resultados con BAP 1 mg/L en fotoperíodo 12:12 (luz: oscuridad). Los tejidos cultivados en fotoperiodo corto, presentaron decoloración y mayor porcentaje de mortalidad

Psychometric properties of a new short version of the State-Trait Anxiety Inventory (STAI) for the assessment of anxiety in the elderly

Introduction: Anxiety has negative effects on the cognitive performance and psychosocial adjustment of elderly people. Given the high prevalence of anxiety symptoms in patients suffering from cognitive impairment, it has been suggested that these symptoms may be an early marker of dementia. The State-Trait Anxiety Inventory (STAI) is one of the widely-used used scales for evaluating anxiety in elderly people. However, inasmuch as the STAI may be difficult to apply to older people, having a short form of it would be desirable. Methods: The participants comprised 489 community-dwelling individuals aged 68 years and over. All of them were volunteers in a longitudinal study for early detection of Alzheimer’ Disease (Proyecto Vallecas). The full sample was divided in two homogeneous subgroups: Group A, used to reduce the number of items and response options, and Group B, the group used to determine the psychometric properties of the new short form (STAIr). Results: A dichotomous Rasch model was used to obtain the STAIr. No statistically significant differences for STAIr scores were found with respect to sociodemographic variables. Psychometric properties and normative data were obtained for the new short-version. Conclusions: The STAIr is composed of 13 items and data fits the model well. Since it is short and easy to apply to elderly people, STAIr will be very useful in clinical and research settings. Resumen: Introducción: La ansiedad tiene efectos negativos sobre el rendimiento cognitivo y el ajuste psicosocial de las personas mayores. Dada la elevada prevalencia de los síntomas de ansiedad en personas con deterioro cognitivo, se ha indicado que podrían ser un marcador precoz de demencia. Una de las pruebas más utilizadas para valorar el nivel de ansiedad en personas mayores es el Inventario de Ansiedad Estado-Rasgo (STAI). No obstante, en la medida en que puede resultar una escala larga para los mayores, sería deseable contar con una versión abreviada de la misma. Métodos: Se reclutó una muestra de 489 participantes mayores de 68 años cognitivamente sanos, todos ellos eran voluntarios en un proyecto de investigación longitudinal sobre la enfermedad de Alzheimer (Proyecto Vallecas). La muestra se subdividió en 2 grupos homogéneos: el grupo A se utilizó para reducir el número de ítems y de opciones de respuesta, y el grupo B para obtener las propiedades psicométricas de la nueva escala reducida (STAIr). Resultados: Se empleó el modelo de Rasch dicotómico para obtener el STAIr. Las variables sociodemográficas no mostraron asociación con las puntuaciones de la nueva versión. Se estudiaron las propiedades psicométricas y se hallaron los datos normativos del STAIr. Conclusiones: La nueva versión STAIr se compone de 13 ítems y presenta una adecuada bondad psicométrica. En la medida en que es una escala rápida y sencilla para las personas mayores, su aplicación resulta útil en los contextos clínico e investigador. Keywords: Anxiety, Cognitive impairment, Ageing, Neuropsychological assessment, State-Trait Anxiety Inventory, Item response theory, Palabras clave: Ansiedad, Deterioro cognitivo, Envejecimiento, Evaluación neuropsicológica, Inventario de Ansiedad Estado-Rasgo, Teoría de respuesta al íte