The multifaceted roles of gasdermins in cancer biology and oncologic therapies

The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/ DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and proinflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical level.This study was supported by the Ministerio de Ciencia e Innovación (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundación Científica de la AECC (FC_AECC PROYE19036MOR -GMB-).S

Prefrontal gray matter and motivation for treatment in cocaine dependent individuals with and without personality disorders

Addiction treatment is a long-term goal and therefore prefrontal–striatal regions regulating goal-directed behavior are to be associated with individual differences on treatment motivation. We aimed at examining the association between gray matter volumes in prefrontal cortices and striatum and readiness to change at treatment onset in cocaine users with and without personality disorders. Participants included 17 cocaine users without psychiatric comorbidities, 17 cocaine users with Cluster B disorders, and 12 cocaine users with Cluster C disorders. They completed the University of Rhode Island Change Assessment Scale, which measures four stages of treatment change (precontemplation, contemplation, action, and maintenance) and overall readiness to change, and were scanned in a 3 T MRI scanner. We defined three regions of interest (ROIs): the ventromedial prefrontal cortex (including medial orbitofrontal cortex and subgenual and rostral anterior cingulate cortex), the dorsomedial prefrontal cortex (i.e., superior medial frontal cortex), and the neostriatum (caudate and putamen). We found that readiness to change correlated with different aspects of ventromedial prefrontal gray matter as a function of diagnosis. In cocaine users with Cluster C comorbidities, readiness to change positively correlated with gyrus rectus gray matter, whereas in cocaine users without comorbidities it negatively correlated with rostral anterior cingulate cortex gray matter. Moreover, maintenance scores positively correlated with dorsomedial prefrontal gray matter in cocaine users with Cluster C comorbidities, but negatively correlated with this region in cocaine users with Cluster B and cocaine users without comorbidities. Maintenance scores also negatively correlated with dorsal striatum gray matter in cocaine users with Cluster C comorbidities. We conclude that the link between prefrontal–striatal gray matter and treatment motivation is modulated by co-existence of personality disorders

Prefrontal gray matter and motivation for treatment in cocaine-dependent individuals with and without personality disorders

Addiction treatment is a long-term goal and therefore prefrontal–striatal regions regulating goal-directed behavior are to be associated with individual differences on treatment motivation. We aimed at examining the association between gray matter volumes in prefrontal cortices and striatum and readiness to change at treatment onset in cocaine users with and without personality disorders. Participants included 17 cocaine users without psychiatric comorbidities, 17 cocaine users with Cluster B disorders, and 12 cocaine users with Cluster C disorders. They completed the University of Rhode Island Change Assessment Scale, which measures four stages of treatment change (precontemplation, contemplation, action, and maintenance) and overall readiness to change, and were scanned in a 3T MRI scanner. We defined three regions of interest (ROIs): the ventromedial prefrontal cortex (including medial orbitofrontal cortex and subgenual and rostral anterior cingulate cortex), the dorsomedial prefrontal cortex (i.e., superior medial frontal cortex), and the neostriatum (caudate and putamen). We found that readiness to change correlated with different aspects of ventromedial prefrontal gray matter as a function of diagnosis. In cocaine users with Cluster C comorbidities, readiness to change positively correlated with gyrus rectus gray matter, whereas in cocaine users without comorbidities it negatively correlated with rostral anterior cingulate cortex gray matter. Moreover, maintenance scores positively correlated with dorsomedial prefrontal gray matter in cocaine users with Cluster C comorbidities, but negatively correlated with this region in cocaine users with Cluster B and cocaine users without comorbidities. Maintenance scores also negatively correlated with dorsal striatum gray matter in cocaine users with Cluster C comorbidities. We conclude that the link between prefrontal–striatal gray matter and treatment motivation is modulated by co-existence of personality disorders

Hemizygous Granzyme A Mice Expressing the hSOD1G93A Transgene Show Slightly Extended Lifespan

Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our work was to assess whether the absence of gzmA in an ALS murine model could help slow down the progression of the disease. Homozygous and hemizygous gzmA-deficient mice expressing the hSOD1G93A transgene were generated, and survival of these mice was monitored. Subsequently, gene and protein expression of inflammatory and oxidative stress markers was measured in the spinal cord and quadriceps of these mice. We observed the longest lifespan in gzmA+/− mice. GzmA gene and protein expression was downregulated in the spinal cord and serum from gmzA+/− mice, confirming that the increased survival of hemizygous mice is correlated with lower levels of gzmA. In addition, mRNA and protein levels of glutathione reductase (GSR), involved in oxidative stress, were found downregulated in the spinal cord and quadriceps of gmzA+/− mice, together with lower IL-1β and IL-6 mRNA levels in hemyzigous mice. In summary, our findings indicate for the first time that reduced levels, but not the absence, of gzmA could slightly ameliorate the disease progression in this animal model

Identificación del Estado Actual del SG-SST - Propuesta De Mejora Para Servimportaciones MS S.A.S

Con base en el Decreto 1072 de 2015 en Colombia, todas las empresas deben implementar un Sistema de Gestión de Seguridad y Salud en el Trabajo, siguiendo estándares mínimos. En este contexto, el objetivo de la investigación en Servimportaciones MS S.A.S. es garantizar la correcta implementación de dicho sistema, proporcionando orientación y capacitación al personal, y cumpliendo con el ciclo PHVA para establecer objetivos, llevar a cabo acciones, verificar el cumplimiento y mejorar continuamente

Concepciones, sentires y particularidades “Sobre el uso de las redes sociales virtuales y las relaciones familiares en los estudiantes del Colegio Distrital República dominicana sede b. Una mirada desde lo cualitativo”

El presente documento es el resultado de una investigación cualitativa de carácter descriptivo, es decir su nivel de alcance es la descripción, basada en un paradigma hermenéutico, con el objetivo de interpretar el uso de las redes sociales virtuales en las relaciones familiares, surge con el fin de hacer un aporte teórico a la disciplina de Trabajo Social ya que se encontró que el presente tema investigado no es un objeto de estudio constante dentro de la academia. En los últimos años, se ha generado un cambio significativo frente a las tecnologías, encontrando un uso masivo de las mismas en la sociedad actual, dichas tecnologías se ven representadas en el uso del internet, en especial de las redes sociales virtuales, por lo tanto, las familias se ven inmersas en este desarrollo tecnológico adaptándose a estas nuevas de formas de comunicación

Tendencias estacionales y anuales en las poblaciones de campo de la mosca mediterránea de la fruta, Ceratitis capitata, en cítricos del Mediterráneo: comparación de dos áreas geográficas en el este de España

[EN] Seasonal and annual trends in Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) populations were analyzed to determine the factors that influence population fluctuations in the field. Adult flies were monitored along 2003-07 in two citrus areas in eastern Spain with similar climate, Valencia and Tarragona. Adults were present throughout the study period, even in winter. The initial annual population increase was related to previous winter and spring temperatures. Captures started to increase in April-May and usually reached a peak in July. This peak corresponded to the maximum capture period in Valencia, but not in Tarragona, where there was usually a second peak in autumn, with capture levels similar to the first peak. Gravid females were found throughout the year, even in overwintering populations of medfly. The availability of other host fruit species in the vicinity of the citrus groves may explain the differences in annual abundance and distribution of captures between the two areas studied.[ES] Se analizó la evolución estacional de las poblaciones de Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) para determinar los factores que influencian sus fluctuaciones poblacionales en campo. Se muestreó la población de adultos entre 2003 y 2007 en dos áreas citrícolas del este de España con clima similar, Valencia y Tarragona. Se encontraron adultos a lo largo de todo el periodo de estudio, incluso en invierno. El primer incremento anual de la población estuvo relacionado con las temperaturas previas del invierno y la primavera. Las capturas comenzaron a incrementarse en abril-mayo y generalmente alcanzaron un máximo en julio. Este máximo correspondió al máximo periodo de capturas en Valencia, pero no en Tarragona, donde hubo generalmente un segundo máximo en otoño, con niveles de captura similares al primer máximo. Se encontraron hembras grávidas a lo largo de todo el año, incluso en las poblaciones invernantes de mosca de la fruta. La disponibilidad de otras especies de frutales hospedantes cercanas a las parcelas de cítricos puede explicar las diferencias en abundancia anual y distribución estacional de capturas entre las dos áreas estudiadas.We would like to thank Rafel Monfort for his help with the field work. This research was funded by a project from the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), of Spain’s Ministerio de Educación y Ciencia (Project RTA03- 103-C6). We thank also Alejandro Tena for useful comments on early drafts of the manuscript.Martinez-Ferrer, MT.; Navarro Campos, C.; Campos Rivela, JM.; Marzal Moreno, C.; Fibla, JM.; Bargues Desolmes, L.; García Mari, F. (2010). Seasonal and annual trends in field populations of Mediterranean fruit fly, Ceratitis capitata, in Mediterranean citrus groves: comparison of two geographic areas in eastern Spain. Spanish Journal of Agricultural Research. 8(3):757-765. https://doi.org/10.5424/sjar/2010083-1275S7577658

Use of Remote Sensing/Geographical Information Systems (RS/GIS) to Identify the Distributional Limits of Soil-Transmitted Helminths (STHs) and Their Association to Prevalence of Intestinal Infection in School-Age Children in Four Rural Communities in Boaco, Nicaragua

STHs can infect all members of a population but school-age children living in poverty are at greater risk. Infection can be controlled with drug treatment, health education and sanitation. Helminth control programs often lack resources and reliable information to identify areas of highest risk to guide interventions and to monitor progress. Objectives: To use RS/GIS to identify the environmental variables that correlate with the ecology of STHs and with the prevalence of STH infections. Methods: Geo-referenced in situ prevalence data will be overlaid over an ecological map derived from the RS environmental data using ESRI s ArcGIS 9.3. Prevalence data and RS environmental data matching at the same geographical location will be analyzed for correlation and those RS environmental variables that better correlate with prevalence data will be included in a multivariate regression model. Temperature, vegetation, and distance to bodies of water will be inferred using data from the Moderate-Resolution Imaging Spectroradiometer (MODIS) onboard the Terra and Aqua satellites, and Thematic Mapper (TM) and Enhance Thematic Mapper Plus (ETM+) satellite sensors onboard Landsat 5 and Landsat 7 respectively. Elevation will be estimated with data from The Shuttle Radar Topography Mission (SRTM). Prevalence and intensity of infections will be determined by parasitological survey (Kato Katz) of children enrolled in rural schools in Boaco, Nicaragua, in the communities of El Roblar, Cumaica Norte, Malacatoya 1, and Malacatoya 2). Expected Results: Associations between RS environmental data and prevalence in situ data will be determined and their applications to public health will be discussed. Discussion/Conclusions: The use of RS/GIS data to predict the prevalence of STH infections could be useful for helminth control programs, providing improved geographical guidance of interventions while increasing cost-effectiveness. Learning Objectives: (1) To identify the RS environmental variables that can help predict the prevalence of STH infections. (2) To understand potential applications of RS/GIS to national helminth control programs. (3) To asses the applicability of RS/GIS to control STH infections

Tuberculine reaction measured by infrared thermography

Setting: The infection with Mycobacterium tuberculosis gives a delayed immune response, measured by the tuberculine skin test. We present a new technique for evaluation based on automatic detection and measurement of skin temperature due to infrared emission.; Design: 34 subjects (46.8+/-16.9 years) (12/22, M/F) with suspected tuberculosis disease were examined with an IR thermal camera, 48h after tuberculin skin injection.; Results: In 20 subjects, IR analysis was positive for tuberculine test. Mean temperature of injection area was higher, around 1 degrees C, for the positive group (36.2+/-1.1 degrees C positive group; 35.1+/-1.6 degrees C negative group, p < 0.02 T test for unpaired groups).; Conclusion: IR image analysis achieves similar estimation of tuberculin reaction as the visual evaluation, based on higher temperature due to increased heat radiation from the skin lesion.Peer ReviewedPostprint (author's final draft

Chromosomal and SRY gene findings by FISH in patients with disorders of sexual development

Objetivo: Los trastornos del desarrollo sexual son un grupo de enfermedades congénitas que afectan la formación normal de los genitales. Dentro los mecanismos fisiopatológicos descritos existen factores genéticos causados por alteraciones cromosómicas o en los genes determinantes en la diferenciación sexual. En este trabajo se analizaron alteraciones cromosómicas y en el gen SRY como posible causa del trastorno. Se realizó cariotipo con bandas G o R y FISH para SRY en linfocitos, tejido gonadal y tejido escrotal. Materiales y métodos: La información clínica de los sujetos de investigación se obtuvo de los informes de los médicos tratantes. En 9 (73%) casos el sexo asignado fue masculino y en 3 (27%) casos fue femenino. 8 de los casos (66%) tuvieron cariotipo 46,XY; 2 casos (17%) 46,XX y en 2 casos (17%) se reportaron mosaicos con presencia de idic(Y). Un solo caso de tejido gonadal mostró mosaicismo debido a la presencia de una línea celular tetraploide. El diagnóstico clínico más frecuente fue de genitales ambiguos en 8 casos (67%). Seguido de hipospadias en 5 casos (41,7%). Conclusiones: Los resultados muestran la importancia de aplicar diferentes pruebas citogenéticas en el diagnóstico y la necesidad del seguimiento de los pacientes por un equipo transdisciplinario para abordar estas condiciones clínicas.Q4Pacientes diagnosticados con trastornos del desarrollo sexualObjective: Disorders of sexual development are a group of congenital diseases that affect the normal formation of genital structures. Within the pathophysiologic mechanisms described, there are genetic factors caused by chromosomal or sex-determining gene alterations. Therefore, chromosomal analysis is an essential priority in the diagnostic approach. Alterations in the chromosomes and the SRY gene as a cause of disorder of sexual development was analyzed herein. Material and methods: G or R-banding karyotype and FISH analyses for the SRY gene were performed in lymphocytes, gonadal tissue, and scrotal tissue in twelve cases, three cases, and one case, respectively. The clinical information was obtained from the patients’ medical reports. Results: In 9 (73%) cases, the assigned sex was male, and in 3 (27%) cases, it was female. Karyotype 46,XY was found in 8 (66%) cases, 46,XX in 2 (17%) cases, and mosaic karyotype in 2 (17%) cases with idic(Y). A single case of gonadal tissue showed mosaicism due to the presence of a tetraploid cell line. The most common clinical diagnosis was abnormal genital differentiation in 8 (67%) cases, followed by hypospadias in 5 (41.7%) cases. Conclusions: The results show the importance of applying different cytogenetic tests in making the diagnosis, and the need for a multidisciplinary team to address the disorder.https://orcid.org/0000-0001-7501-7307https://orcid.org/0000-0002-0729-6866https://orcid.org/0000-0002-1421-3619https://orcid.org/0000-0001-6336-5347https://orcid.org/0000-0001-8528-4433https://orcid.org/0000-0002-2231-4321https://orcid.org/0000-0002-7856-7213https://orcid.org/0000-0003-2241-7854https://orcid.org/0000-0002-9675-5963https://orcid.org/0000-0001-5685-8354https://orcid.org/0000-0002-0826-6191Revista Internacional - IndexadaCN