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International audience; Bistable molecules represent a potential miniaturization limit for high-density information technologies. However, molecules exhibit memory effect typically at very low temperatures. This is the case of spin-crossover (SCO) complexes, where the concept of a molecular memory has not been considered due to the fast spin-state interconversion of all previous systems. Breaking this principle, here we report a slow relaxation process found in an SCO iron-triazole polyanionic complex. Multiple experimental evidences confirm the opening of a thermal hysteresis upon solid dilution and even in liquid solution. Density functional theory (DFT) calculations reveal the origin of this unexpected phenomenon to the appearance of an energy barrier that slows down the spin-state relaxation processes at the molecular level. These results show how SCO molecules may store information at room temperature, opening unique opportunities for molecular data storage.

Resumen Introduccion y objetivos Los nodulos tiroideos requieren con frecuencia evaluacion mediante ecografia y puncion aspiracion con aguja fina (PAAF). No obstante, la PAAF no permite la diferenciacion entre adenoma y carcinoma folicular en lesiones de tipo IV segun la clasificacion de Bethesda. Esto provoca numerosas intervenciones quirurgicas innecesarias porque no es posible garantizar el caracter benigno de las lesiones, ni siquiera cuando la mayoria de las muestras corresponden a adenomas o incluso a otras lesiones benignas. El objetivo de este estudio es establecer si hay caracteristicas ecograficas que nos ayudarian a pronosticar el riesgo de malignidad de los nodulos con un diagnostico anatomopatologico de neoplasia folicular para conseguir un abordaje mas conservador de los nodulos sin sospecha de malignidad. Material y metodos Estudiamos 61 nodulos en 61 pacientes (51 mujeres y 10 varones) que se habian sometido a intervencion quirurgica de la glandula tiroides y tenian resultados histopatologicos de adenoma o carcinoma folicular. Se analizaron diversas caracteristicas ecograficas de los nodulos (composicion, ecogenicidad, borde, estado de calcificacion, presencia de halo y sospecha general de malignidad segun el observador) y se establecio su correlacion con el analisis histopatologico. Resultados Observamos una relacion estadisticamente significativa entre el carcinoma folicular y la presencia de calcificaciones, bordes mal definidos y la sospecha o impresion general del observador (definida por sospecha clara de signos ecograficos de malignidad, como calcificacion, borde mal definido y un nodulo solido marcadamente hipoecoico; y signos ecograficos de benignidad, como composicion ecogenica predominantemente quistica y presencia de halo hipoecogenico perinodular). Sin embargo, todas estas caracteristicas han mostrado una sensibilidad baja en el estudio que nos ocupa (30%, 30% y 50%, respectivamente). En cambio, la ausencia del signo de halo ha demostrado una sensibilidad del 100% y un valor predictivo negativo del 100% en nuestro estudio. Conclusiones La presencia de calcificaciones, los bordes mal definidos y la impresion o sospecha general de malignidad se asocian con un riesgo mayor de carcinoma folicular en nodulos tiroideos de tipo IV segun la clasificacion de Bethesda, pero su ausencia no permite pronosticar el caracter benigno de estos nodulos. En cambio, cuando se observa una lesion con signo de halo, deberia considerarse una neoplasia folicular benigna.

The opioid crisis was exacerbated during the COVID-19 pandemic in the United States with alarming statistics about overdose-related deaths. Current treatment options, such as medication assisted treatments, have been unable to prevent relapse in many patients, whereas cue-based exposure therapy have had mixed results in human trials. To improve patient outcomes, it is imperative to develop animal models of addiction to understand molecular mechanisms and identify potential therapeutic targets. We previously found increased brain derived neurotrophic factor (bdnf) transcript in the ventral striatum/nucleus accumbens (VS/NAc) of rats that extinguished morphine-induced place preference. Here, we expand our study to determine whether BDNF protein expression was modulated in mesolimbic brain regions of the reward system in animals exposed to extinction training. Drug conditioning and extinction sessions were followed by Western blots for BDNF in the hippocampus (HPC), amygdala (AMY) and VS/NAc. Rears, as a measure of withdrawal-induced anxiety were also measured to determine their impact on extinction. Results showed that animals who received extinction training and successfully extinguished morphine CPP significantly increased BDNF in the HPC when compared to animals deprived of extinction training (sham-extinction). This increase was not significant in animals who failed to extinguish (extinction-resistant). In AMY, all extinction-trained animals showed increased BDNF, regardless of behavior phenotype. No BDNF modulation was observed in the VS/NAc. Finally, extinction-trained animals showed no difference in rears regardless of extinction outcome, suggesting that anxiety elicited by drug withdrawal did not significantly impact extinction of morphine CPP. Our results suggest that BDNF expression in brain regions of the mesolimbic reward system could play a key role in extinction of opioid-induced maladaptive behaviors and represents a potential therapeutic target for future combined pharmacological and extinction-based therapies.

The percentage of patients with metastatic non-small cell lung cancer (NSCLC) and melanoma who benefit from anti-programmed cell death protein 1 (anti-PD-1) is low owing to resistance mechanisms. SABR has a role in oligoprogressive disease and can improve responses to anti-PD-1. This multicenter prospective observational study aimed to determine whether concomitant anti-PD-1 and SABR to oligoprogressive sites enhance tumor response in metastatic NSCLC and melanoma.Patients with metastatic NSCLC or melanoma in progression to anti-PD-1 but continuing the same line owing to clinical benefit were referred for palliative SABR. All patients received concomitant pembrolizumab or nivolumab and SABR to 1 to 5 lesions, maintaining anti-PD-1 until further progression, unacceptable toxicity, or medical/patient decision. Objective response rate-complete responses and partial responses-was evaluated during all follow-up according to Response Evaluation Criteria in Solid Tumors 1.1. The abscopal response was evaluated 8 weeks after SABR as a ≥30% reduction in 1 to 2 predefined nonirradiated lesions.Of the 61 patients enrolled, 50 could be analyzed. With a median follow-up of 32.8 months, objective response rate was 42% (30% complete responses and 12% partial responses). Median progression-free survival was 14.2 months (95% confidence interval, 6.9-29 months). Median overall survival since SABR was 37.4 months (95% confidence interval, 22.9 months-not reached). Abscopal response was 65%, evaluated in 40 patients who fulfilled the criteria.Combined anti-PD-1 and SABR in oligoprogressive metastatic NSCLC or melanoma can achieve high rates of response and extend the clinical benefit of immunotherapy by delaying further progression and a new systemic therapy. This approach should be assessed in larger randomized trials.

In press., [ES]: [Introducción]: La povidona yodada y el peróxido de hidrógeno podrían ser eficaces contra el SARS-CoV-2. [Métodos]: Estudio observacional de seguimiento prospectivo (EPA-AS) en 88 pacientes (43 ± 17 años, 55% varones) con SARS-CoV-2 en muestras nasofaríngeas (RT-PCR). Treinta y uno recibieron enjuagues/gargarismos con povidona yodada cada 8 h 2 días consecutivos, 17 con la misma pauta de peróxido de hidrógeno y 40 controles sin enjuagues. Se repitió PCR a los 3, 11 y 17 días. [Resultados]: Tras la intervención no hubo diferencias en la carga viral: povidona yodada (4,3 ± 2,7 copias/ml), peróxido de hidrógeno (4,6 ± 2,9 copias/ml), controles (4,4 ± 3,0 copias/ml). El porcentaje de pacientes con una 2.ª PCR negativa fue 27% povidona yodada, 23% peróxido de hidrógeno y 32% controles; en la 3.ª PCR 62%, 54% y 58% respectivamente y en la 4.ª PCR, 81%, 75% y 81%. [Conclusión]: Nuestros resultados no apoyan la utilidad de los enjuagues de estos 2 antisépticos en pacientes con COVID-19., [EN]: [Introduction]: Povidone-iodine and hydrogen peroxide could be effective in against SARS-CoV-2. [Methods]: A “non-interventional trial” in 88 patients (43 ± 17 yrs, 55% men) with SARS-CoV-2 in nasopharyngeal swabs (RT-PCR). 31 received mouth rinses/gargling with povidone-iodine (every 8 h, two consecutive days), 17 with mouth rinses/gargling of hydrogen peroxide, and 40 controls. PCR were repeated at 3, 11 and 17 days. [Results}: After intervention the viral load (Log 10 copies/ml) remained similar in povidone-iodine (4.3 ± 2.7 copies/ml), hydrogen peroxide (4.6 ± 2.9 copies/ml; p = 0.40) and controls (4.4 ± 3.0 copies/ml). The percentage of patients with a negative result in the second PCR was 27% in povidone-iodine group, 23% in hydrogen peroxide and 32% in controls; in the third PCR, 62%, 54% and 58% respectively; and in the fourth PCR, 81%, 75% and 81%. [Conclusion]: Our results do not support the clinical usefulness of mouth rinses/gargling with povidone-iodine or hydrogen peroxide in patients with COVID-19., Este trabajo ha sido financiado con una Beca de Investigación otorgada por el Consejo Superior de Investigaciones Científicas (CSIC. 202050E106). España.