Implicación de la proteína clusterina y la actividad apoptótica en la transformación maligna y el pronóstico de los pacientes con cáncer colorrectal

Introducción: La carcinogénesis colorrectal es un proceso de múltiples etapas que progresa desde el tejido normal a adenoma y finalmente carcinoma. Se ha relacionado a la clusterina (CLU), una glicoproteína heterodimérica ampliamente distribuida en el organismo de los mamíferos, con la supervivencia celular, la respuesta al estrés y la resistencia a los tratamientos antineoplásicos. De hecho, existen terapias anti-CLU con oliglonucleótidos antisentido capaces de potenciar la apoptosis inducida por los citotóxicos convencionales. Sin embargo, la evidencia disponible sobre la participación de CLU en la progresión tumoral del colon es limitada y poco sabemos acerca de su valor pronóstico en el cáncer colorrectal (CCR). Además, el papel que juega la apoptosis en esta secuencia de carcinogénesis colorrectal no ha sido completamente clarificado, y los trabajos que han investigado la relación entre la actividad apoptótica y la supervivencia de los pacientes con CCR han arrojado resultados, hasta la fecha, contradictorios. Objetivos: Los objetivos del estudio fueron estudiar la relación de CLU con la carcinogénesis y la progresión tumoral del CCR, así como su significado pronóstico, analizando el impacto de la expresión de CLU en la supervivencia de los pacientes con CCR. Asimismo, se quiso determinar la influencia de la actividad apoptótica en la carcinogénesis y el pronóstico del CCR. Material y Métodos: Examinamos las muestras de 103 CCRs resecados en el Hospital Costa del Sol, 31 adenomas y 20 epitelios normales. CLU se determinó mediante inmunohistoquímica, usando un anticuerpo monoclonal anti-cadena α (Upstate-Millipore, Watford, Inglaterra). La expresión de CLU fue considerada negativa (CLU-) si no se observaba tinción y positiva (CLU+) cuando >10% de células resultaban teñidas. Para la detección de la apoptosis. se llevó a cabo el ensayo TUNEL. La media de porcentaje apoptótico (1%, rango 0-6%) fue el punto de corte empleado para los estudios de supervivencia. La estimación de la supervivencia se hizo mediante el método de Kaplan-Meier y usamos la regresión de Cox para el análisis multivariante (nivel de significación estadística p<0.05). La mediana de seguimiento fue 54 meses. La mediana de edad fue 70 años (rango 45-91) y la distribución por estadios: I (15%), II (48%), III (23%) y IV (14%). Resultados: Las células epiteliales del tejido normal fueron CLU-. En cambio el 16% (5/31) de los adenomas fue CLU+ y este porcentaje se incrementó en los CCRs (30%, 31/103). Las recidivas fueron más frecuentes en los tumores CLU+ (61%,19/31) que en los CLU- (37%, 27/72) y la expresión de CLU se asoció significativamente con una menor supervivencia libre de progresión (SLP) (SLP a 5 años: 35 ± 9% vs 57 ± 7%; p 0.03). En el análisis multivariante, CLU (HR=2.01, IC 95% 1.03-3.90) y el estadio TNM (HR=2.20; IC 95% 1.13-4.29) fueron factores pronósticos independentes para la SLP. Encontramos un índice apoptótico (IA) mayor en los CCRs (1.09 ± 0.13) que en los adenomas (0.38 ± 0.23, p=0.059) y significativamente mayor que en el epitelio normal (0.06 ± 0.04, p=0.001). El estadio IV mostró un IA superior en comparación con otros estadios (p=0.017). El IA alto se asoció con una menor SLP (SLP a 5 años: 28.5 ± 9.6% vs 61.8 ± 8.1%; p<0.05) y supervivencia global (SG) (SG a 5 años: 43.7 ± 11.9% vs 74.6 ± 8.8%; p <0.05). En el análisis multivariante, el IA (HR=2.18, IC 95% 1.08-4.37) y el estadio TNM (HR=2.41, 95% CI 1.20-4.85) resultaron factores pronósticos independientes para la SG. Conclusiones: Tanto CLU como la actividad apoptótica aumentan progresivamente a lo largo de la secuencia mucosa sana-adenoma-carcinoma, lo que sugiere un papel relevante en la carcinogénesis colorrectal. La sobreexpresión de CLU se asocia con un peor pronóstico de los pacientes con CCR, por lo que nos permite identificar a pacientes con tumores de comportamiento más agresivo. Un IA elevado se asocia también con una mayor agresividad tumoral y una peor supervivencia del CCR

First Record of Streptocara formosensis (Nematoda: Acuariidae) from the Chubut Steamerduck, Tachyeres leucocephalus, Endemic to the Patagonian Coast, Southwest Atlantic

Streptocara formosensis (Nematoda: Acuariidae) is recorded for the first time from South America (Chubut Province, Argentina) and from the Chubut steamerduck, Tachyeres leucocephalus (Aves: Anatidae), enlarging its host and geographical distribution. To our knowledge, this is the first record of a parasite in this bird species.Fil: Aguero Alcaide, Maria Laura Gema. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Diaz, Julia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Estudios Parasitológicos y de Vectores (i); Argentin

Testing PtCu nanoparticles supported on highly ordered mesoporous carbons CMK3 and CMK8 as catalysts for low-temperature fuel cells

Pt(Cu) nanoparticles supported on CMK3 and CMK8 ordered mesoporous carbons (OMCs) have been synthesized by electroless deposition of Cu followed by galvanic exchange with Pt. The structural characterization by high-resolution transmission electron microscopy and X-ray diffraction showed the formation of Pt(Cu) nanoparticles of 4-5 nm, in which PtCu alloys with contracted fcc Pt lattice and 70-80 at.% Pt was identified. The X-ray photoelectron spectroscopy analyses indicated that the Pt(Cu) nanoparticles were mainly composed of a PtCu alloy core covered by a Ptrich shell, in agreement with the steady cyclic voltammograms, which did not show any Cu oxidation peaks. Electroactive surface areas up to about 70 m2 gPt−1 were obtained. The onset potentials for CO oxidation and the oxygen reduction reaction were more negative and positive, respectively, as compared to Pt/C, thus indicating higher activity of these Pt(Cu) catalysts with respect to the latter. Based on the corresponding binding energies, these better activities were attributed to the favorable geometric and ligand effects of Cu on Pt, which were able to reduce the adsorption energy of the intermediates on Pt. Pt(Cu)/CMK3 showed competitive mass and specific activities, as well as better stability than Pt/C

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021)

Diagnosis; Esophageal cancer; TreatmentDiagnóstico; Cáncer de esófago; TratamientoDiagnòstic; Càncer d'esòfag; TractamentEsophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care

Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV + neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females

Developing a model to predict the early risk of hypertriglyceridemia based on inhibiting lipoprotein lipase (LPL): a translational study

Hypertriglyceridemia; Inhibiting lipoprotein lipaseHipertrigliceridèmia; Inhibició de la lipoproteïna lipasaHipertrigliceridemia; Inhibición de la lipoproteína lipasaHypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches.This research was financially supported by the Catalan Government through the funding grant ACCIÓ-Eurecat (PRIV2019-PREVENTOMICS) and by the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation under grant agreement: TECNOMIFOOD project. CER-20191010

COVID-19 en los Centros Municipales de Servicios Sociales de Zaragoza

El presente trabajo es un estudio sobre el impacto que ha tenido la COVID-19 en los Centros Municipales deServicios Sociales de Zaragoza (CMSS). En particular, este estudio analiza los cambios respecto a las personasusuarias, la organización de los CMSS y los/as profesionales. Para alcanzar dicho objetivo se ha realizado unainvestigación cualitativa a partir de nueve entrevistas semiestructuradas a trabajadoras sociales de los CMSS.El análisis de contenido revela que el volumen de personas usuarias atendidas ha aumentadoconsiderablemente durante el estado de alarma habiendo requerido este aumento un mayor número deatenciones. Además, la pandemia ha modificado el perfil de las personas usuarias y ha acentuado lavulnerabilidad de los que ya se encontraban incluidos en el sistema. Los CMSS han estado sobrecargadosdurante este periodo, debido sobre todo al aumento de la demanda, las bajas laborales sin cubrir y elaumento de los trámites administrativos.<br /

Electrochemical performance of carbon-supported Pt(Cu) electrocatalysts for low-temperature fuel cells

Pt(Cu) nanoparticles supported on carbon nanofibers (CNFs), multi-walled carbon nanotubes (MWCNTs) and Vulcan carbon XC72, have been synthesized by electroless deposition and galvanic exchange. The structural analyses show contracted Pt fcc lattices due to the formation of a PtCu alloy core covered by a Pt-rich shell, mean crystallite sizes of about 3 nm, as well as good dispersion and carbon attachment. The electrochemical surface areas (ECSAs) of Pt(Cu)/CNF and Pt(Cu)/XC72 are comparable to those of commercial Pt/C and PtCu/C. The Pt(Cu) electrocatalysts show more negative onset potentials for CO oxidation than Pt/C and PtCu/C, thus indicating their greater CO tolerance. Pt(Cu)/CNF and Pt(Cu)/MWCNT present the highest mass activity and specific activity for the O2 reduction, respectively, both with better relative stability than Pt(Cu)/XC72. Pt(Cu)/CNF and Pt(Cu)/MWCNT are then considered good cathode catalysts, yielding estimated savings of about 50 wt.% Pt, when applied to low-temperature fuel cells

On the viability of chitosan-derived mesoporous carbons as supports for PtCu electrocatalysts in PEMFC

Chitosan is an abundant and non-toxic natural polysaccharide rich in nitrogen, which is used here to obtain N-doped mesoporous carbons (NMCs) as supports for Pt-saving PtCu alloy elecrocatalysts, which can be of interest for low-temperature fuels cells. NMCs with different textural properties were synthesized from cheap silica templates. They presented relative dominance of disordered graphitic lattice and comparable amounts of pyrrolic and pyridinic N, with different specific BET surface areas (715-1040 m2 g−1) and mesopore (1.2-2.4 cm3 g−1) and micropore volumes (0.1-0.6 cm3 g−1). PtCu nanoparticles were deposited by Cu electroless deposition and further galvanic exchange with Pt, with overall Pt loadings about 20 wt.%. Pt-rich PtCu alloy crystallites with contracted Pt fcc lattices and sizes of 3.1-4.7 nm were formed. The synthesized PtCu/NMCs catalysts presented better specific current densities for the oxygen reduction and better CO tolerance and specific current densities for the methanol oxidation reaction than those of commercial Pt/C and PtCu/CMK-3. The PtCu/NMC prepared with the H2SO4-activated NMC was the most active catalyst. The different textural properties of the carbonaceous materials appeared to determine the surface structure of the PtCu nanoparticles

The Poly I:C maternal immune stimulation model shows unique patterns of brain metabolism, morphometry, and plasticity in female rats

Introduction: Prenatal infections are associated with an increased risk of the onset of schizophrenia. Rodent models of maternal immune stimulation (MIS) have been extensively used in preclinical studies. However, many of these studies only include males, omitting pathophysiological features unique to females. The aim of this study is to characterize the MIS model in female rats using positron emission tomography (PET), structural magnetic resonance imaging (MR), and neuroplasticiy studies. Methods: In gestational day 15, Poly I:C (or Saline) was injected into pregnant Wistar rats to induce the MIS model. Imaging studies: [18F]-fluoro-2-deoxy-D-glucose-PET scans of female-offspring were acquired at post-natal day (PND) 35 and PND100. Furthermore, T2-MR brain images were acquired in adulthood. Differences in FDG uptake and morphometry between groups were assessed with SPM12 and Regions of Interest (ROI) analyses. Ex vivo study: The density of parvalbumin expressing interneurons (PV), perineuronal nets (PNN), and parvalbumin expressing interneurons surrounded by perineuronal nets (PV-PNN) were evaluated in the prelimbic cortex and basolateral amygdala using confocal microscopy. ROIs and neuroplasticity data were analyzed by 2-sample T-test and 2-way-ANOVA analyses, respectively. Results: A significant increase in brain metabolism was found in all animals at adulthood compared to adolescence. MIS hardly modified brain glucose metabolism in females, highlighting a significant hypometabolism in the thalamus at adulthood. In addition, MIS induced gray matter (GM) enlargements in the pituitary, hippocampus, substantia nigra, and cingulate cortex, and GM shrinkages in some thalamic nuclei, cerebelar areas, and brainstem. Moreover, MIS induced white matter shrinkages in the cerebellum, brainstem and corpus callosum, along with cerebrospinal fluid enlargements in the lateral and 4th ventricles. Finally, MIS reduced the density of PV, PNN, and PV-PNN in the basolateral amygdala. Conclusion: Our work showed in vivo the differential pattern of functional and morphometric affectation in the MIS model in females, as well as the deficits caused at the synaptic level according to sex. The differences obtained highlight the relevance of including both sexes in psychiatric research in order to consider their pathophysiological particularities and successfully extend the benefits obtained to the entire patient population.MS-M was supported by the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (PI17/01766, BA21/0030); co-financed by European Regional Development Fund (ERDF), “A way to make Europe”; project PID2021_128862OB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM; project number CB07/09/0031); Delegación del Gobierno para el Plan Nacional sobre Drogas (project number 2017/085); and Fundación Alicia Koplowitz. MC-V was supported by Fundación Tatiana Pérez de Guzmán el Bueno as scholarship holder of this institution, and EU Joint Programme—Neurodegenerative Disease Research (JPND). DR-M was supported by Consejería de Educación e Investigación, Comunidad de Madrid, co-funded by European Social Fund “Investing in your future” (grant number PEJD-2018-PRE/BMD-7899). NL-R was supported by Instituto de Investigación Sanitaria Gregorio Marañón, “Programa Intramural de Impulso a la I+D+I 2019”. MD’s work was supported by Ministerio de Ciencia e Innovación (MCIN) and Instituto de Salud Carlos III (PT20/00044). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). JN was supported by the project RTI2018-098269-B-I00 and PID2021-127595OB-I00 financed by the Spanish Ministry of Science and Innovation/AEI/10.13039/501100011033/(“FEDER Una manera de hacer Europa”) and the Generalitat Valenciana (PROMETEU/2020/024)