Effects of ketosis on cocaine-induced reinstatement in male mice;

In recent years, the benefits of the ketogenic diet (KD) on different psychiatric disorders have been gaining attention, but the substance abuse field is still unexplored. Some studies have reported that palatable food can modulate the rewarding effects of cocaine, but the negative metabolic consequences rule out the recommendation of using it as a complementary treatment. Thus, the main aim of this study was to evaluate the effects of the KD on cocaine conditioned place preference (CPP) during acquisition, extinction, and reinstatement. 41 OF1 male mice were employed to assess the effects of the KD on a 10 mg/kg cocaine-induced CPP. Animals were divided into three groups: SD, KD, and KD after the Post-Conditioning test. The results revealed that, while access to the KD did not block CPP acquisition, it did significantly reduce the number of sessions required to extinguish the drug-associated memories and it blocked the priming-induced reinstatement. © 2022 The Author(s

Caracterización conductual y neuroinmune de la resiliencia al estrés social: Efectos reforzantes de la cocaína

Numerosos estudios preclínicos han demostrado que el estrés social incrementa la vulnerabilidad a los efectos reforzantes de la cocaína. Sin embargo, los resultados obtenidos no son homogéneos, observándose siempre una subpoblación que no muestra dicho incremento. Utilizando el modelo de derrota social (DS) repetida en ratones, en este trabajo hemos querido caracterizar conductualmente a los ratones resilientes al incremento de los efectos reforzantes de la cocaína inducido por el estrés social. Utilizamos ratones adultos macho de la cepa C57/BL6 a los que sometimos al protocolo de DS repetida y tres semanas más tarde, realizamos el Condicionamiento de Preferencia de Lugar (CPL) inducido por una dosis no efectiva de cocaína (1mg/kg). Una vez finalizado este procedimiento se midieron los niveles estriatales de interleucina 6, ya que el estrés social produce una respuesta de neuroinflamación. No se observó CPL en los ratones controles, pero los animales derrotados tomados en conjunto desarrollaron preferencia. Sin embargo, esta muestra se pudo dividir en ratones resilientes (no desarrollaron preferencia) y susceptibles (presentaron CPL). Durante las derrotas sociales, los animales resilientes pasaron menos tiempo en las conductas de huida y sumisión que los catalogados como susceptible y presentaron conductas de ataque hacia el ratón residente, manifestando por tanto resistencia a ser derrotados. No se observaron diferencias en la respuesta de neuroinflamación, probablemente debido al largo periodo de tiempo trascurrido desde la última derrota social. Nuestros resultados sugieren que un estilo de afrontamiento activo al estrés social va a ser determinante en la protección del sujeto a desarrollar un trastorno por uso de drogas. Preclinical studies have shown that social stress increases vulnerability to the reinforcing effects of cocaine. However, the results are not always homogeneous, revealing a subpopulation that does not show a preference for cocaine. Thus, the main aim of the present study was to characterize the behavioral profile of resilient mice to the stress-induced rewarding effects of cocaine using an animal model of repeated social defeat stress (SD). To this end, male adult mice of the C57/BL6 strain were exposed to SD and, three weeks later, assessed using the Conditioned Place Preference paradigm induced by an ineffective dose of cocaine (1mg/kg). Afterwards, the striatal levels of interleukin 6 were measured, as social stress usually induces a neuroinflammatory response. Control mice did not develop CPP, while defeated mice did overall develop a preference for the drug-paired compartment. Based on the conditioning score that they exhibited, the SD sample was subdivided into resilient (did not develop preference) and susceptible mice (developed preference). During the SD sessions, resilient animals showed less flight and submission behaviors than susceptible mice and they presented attack behaviors towards the residents, thereby showing their resistance to being defeated. There were no differences in the neuroinflammatory response, probably due to the long time elapsed after the last SD session. These results suggest that an active coping style to social stress may be decisive in protecting the individual from developing an addiction. © 2021, Edita Socidrogalcohol. All rights reserved

A Simulation Study of an Inverse Controller for Closed and Semiclosed-Loop Control in Type 1 Diabetes

Background: Closed-loop control algorithms in diabetes aim to calculate the optimum insulin delivery to maintain the patient in a normoglycemic state, taking the blood glucose level as the algorithm's main input. The major difficulties facing these algorithms when applied subcutaneously are insulin absorption time and delays in measurement of subcutaneous glucose with respect to the blood concentration. Methods: This article presents an inverse controller (IC) obtained by inversion of an existing mathematical model and validated with synthetic patients simulated with a different model and is compared with a proportional-integral-derivative controller. Results: Simulated results are presented for a mean patient and for a population of six simulated patients. The IC performance is analyzed for both full closed-loop and semiclosed-loop control. The IC is tested when initialized with the heuristic optimal gain, and it is compared with the performance when the initial gain is deviated from the optimal one (±10%). Conclusions: The simulation results show the viability of using an IC for closed-loop diabetes control. The IC is able to achieve normoglycemia over long periods of time when the optimal gain is used (63% for the full closed-loop control, and it is increased to 96% for the semiclosed-loop control

Reduced salivary oxytocin after an empathic induction task in intimate partner violence perpetrators: importance of socio-affective functions and its impact on prosocial behavior

Intimate Partner Violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial behavior. Thus, the study of salivary OXT (sOXT) may provide further information about potential impairments in social cognition in IPV perpetrators. This study analyzed the effects of an empathic induction task, performed through negative emotion-eliciting videos, on endogenous sOXT levels, mood state, and emotional perception in 30 IPV perpetrators compared to 32 controls. Additionally, we explored their performance on prosocial behavior after the empathic induction task, using Hare's donation procedure. Lower sOXT levels were found in IPV perpetrators after the task compared to controls, along with a general decreasing tendency in their sOXT levels. Additionally, IPV perpetrators exhibited no change in their mood state and perceived others' emotions as more positive and less intense. Moreover, the mood state response and alexithymia traits, respectively, positively and negatively predicted the sOXT levels after the empathic induction task in the entire sample. Finally, we did not observe a lower appearance of prosocial behaviors in IPV perpetrators; however, higher sOXT levels after the empathic induction task were found in subjects who donated when considering the whole sample. In sum, IPV perpetrators exhibited differences in their sOXT levels when empathizing, compared to controls, with alexithymia and the emotional response potentially explaining the sOXT levels after the task. Furthermore, prosocial behavior was more related to these sOXT levels than to IPV. As our knowledge about the emotional processing of IPV perpetrators increases, we will be better able to develop and include coadjutant treatments in current psychotherapeutic programs, in order to focus on their emotional needs, which, in turn, would reduce the future risk of recidivism

Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

Alzheimer’s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment. Copyrigh

El consumo de dieta grasa en forma de atracón durante la adolescencia incrementa los efectos reforzantes del alcohol en ratones macho

Poster presentado al congreso de patología dual en madrid en abril de 2018

El estrés social produce ansiedad e incrementa los efectos reforzantes de la cocaína: utilidad de los antiinflamatorios

poster presentado al congreso de patología dual en madrid en abril de 201

Productivity trends and collaboration patterns: A diachronic study in the eating disorders field

[EN] Objective The present study seeks to extend previous bibliometric studies on eating disorders (EDs) by including a time-dependent analysis of the growth and evolution of multi-author collaborations and their correlation with ED publication trends from 1980 to 2014 (35 years). Methods Using standardized practices, we searched Web of Science (WoS) Core Collection (WoSCC) (indexes: Science Citation Index-Expanded [SCIE], & Social Science Citation Index [SSCI]) and Scopus (areas: Health Sciences, Life Sciences, & Social Sciences and Humanities) to identify a large sample of articles related to EDs. We then submitted our sample of articles to bibliometric and graph theory analyses to identify co-authorship and social network patterns. Results We present a large number of detailed findings, including a clear pattern of scientific growth measured as number of publications per five-year period or quinquennium (Q), a tremendous increase in the number of authors attracted by the ED subject, and a very high and steady growth in collaborative work. Conclusions We inferred that the noted publication growth was likely driven by the noted increase in the number of new authors per Q. Social network analyses suggested that collaborations within ED follow patters of interaction that are similar to well established and recognized disciplines, as indicated by the presence of a ¿giant cluster¿, high cluster density, and the replication of the ¿small world¿ phenomenon¿the principle that we are all linked by short chains of acquaintances.This work was performed with a subsidy from Universidad Catolica de Valencia "San Vicente Martir" to resarch group INDOTEI: Evaluacion de la Ciencia, for the years 2016-2017. This work is benefited from Spanish Government assistance through Government Delegation for the National Drugs Plan of the Ministry of Health, Social Services and Equality (project 2016/028); and National R+D+I (projects: CS02012-39632-C02-01 and CS02015-65594-C2-2-R) and 2015-Networks of Excellence Call (project CS02015-71867-REDT) of the Ministry of Economy and Competitiveness.Valderrama Zurian, JC.; Aguilar-Moya, R.; Cepeda-Benito, A.; Melero-Fuentes, D.; Navarro-Moreno, MÁ.; Gandía-Balaguer, A.; Aleixandre-Benavent, R. (2017). Productivity trends and collaboration patterns: A diachronic study in the eating disorders field. PLoS ONE. 12(8):1-17. https://doi.org/10.1371/journal.pone.0182760S117128McClelland, J., Bozhilova, N., Campbell, I., & Schmidt, U. (2013). A Systematic Review of the Effects of Neuromodulation on Eating and Body Weight: Evidence from Human and Animal Studies. 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Neurosurgical emergency management during the lockdown period in health care regions in Spain with different COVID-19 impact: lessons learned to improve outcomes on the future waves

Background COVID-19 has overloaded health care systems, testing the capacity and response in every European region. Concerns were raised regarding the impact of resources’ reorganization on certain emergency pathology management. The aim of the present study was to assess the impact of the outbreak (in terms of reduction of neurosurgical emergencies) during lockdown in different regions of Spain. Methods We analyzed the impact of the outbreak in four different affected regions by descriptive statistics and univariate comparison with same period of two previous years. These regions differed in their incidence level (high/low) and in the time of excess mortality with respect to lockdown declaration. That allowed us to analyze their influence on the characteristics of neurosurgical emergencies registered for every region. Results 1185 patients from 18 neurosurgical centers were included. Neurosurgical emergencies that underwent surgery dropped 24.41% and 28.15% in 2020 when compared with 2019 and 2018, respectively. A higher reduction was reported for the most affected regions by COVID-19. Non-traumatic spine experienced the most significant decrease in number of cases. Life-threatening conditions did not suffer a reduction in any health care region. Conclusions COVID-19 affected dramatically the neurosurgical emergency management. The most significant reduction in neurosurgical emergencies occurred on those regions that were hit unexpectedly by the pandemic, as resources were focused on fighting the virus. As a consequence, life-threating and non-life-threatening conditions’ mortality raised. Results in regions who had time to prepare for the hit were congruent with an organized and sensible neurosurgical decision-making.Peer reviewe

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products