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One of the major challenges of cocaine addiction is the high rate of relapse to drug use after periods of withdrawal. During the first few weeks of withdrawal, cue-induced cocaine craving intensifies, or "incubates," and persists over extended periods of time. Although several brain regions and molecular mechanisms were found to be involved in this process, the underlying epigenetic mechanisms are still unknown. Herein, we used a rat model of incubation of cocaine craving, in which rats were trained to self-administer cocaine (0.75 mg/kg, 6h/d, 10d), and cue-induced cocaine-seeking was examined in an extinction test after 1 or 30 d of withdrawal. We show that the withdrawal periods, as well as cue-induced cocaine seeking, are associated with broad, time-dependent enhancement of DNA methylation alterations in the nucleus accumbens (NAc). These gene methylation alterations were partly negatively correlated with gene expression changes. Furthermore, intra-NAc injections of a DNA methyltransferase inhibitor (RG108, 100μM) abolished cue-induced cocaine seeking on day 30, an effect that persisted 1 month, whereas the methyl donor S-adenosylmethionine (500μM) had an opposite effect on cocaine seeking. We then targeted two proteins whose genes were demethylated by RG108-estrogen receptor 1 (ESR1) and cyclin-dependent kinase 5 (CDK5). Treatment with an intra-NAc injection of the ESR1 agonist propyl pyrazole triol (10 nM) or the CDK5 inhibitor roscovitine (28μM) on day 30 of withdrawal significantly decreased cue-induced cocaine seeking. These results demonstrate a role for NAc DNA methylation, and downstream targets of DNA demethylation, in incubation of cocaine craving. [ABSTRACT FROM AUTHOR]

Introduction: Planning the future national hospitalization system requires consideration of demographic trends, innovative treatments and policy approaches. The existing situation alone does not allow proper planning in extremely dynamic systems that operate within the framework of scarce resources., Objectives: To identify managers' attitudes regarding hospital planning, deployment and managerial mechanisms in comparison with evidence in the literature., Methods: A survey among hospital managers following a focused conference., Results: Of the 50 respondents, half of the group thought that a general hospital should include 900-2000 beds. The majority prefer an autonomous management style, or a cluster of only a few hospitals. In a scenario of overload and shortage of beds, the majority prefer adding beds to the existing hospital, while about a quarter of the respondents suggest establishing another hospital in the area, or merging nearby hospitals. About half supported home care, or transferring patients to a nearby hospital, including in the private sector, or the transfer of appropriate patients to chronic care institutions. About a third of the respondents supported telemedicine. In terms of national deployment, the preference was that the hospital should be located in high population areas and able to provide sufficient geographical accessibility. Yet, 60% of participants emphasized the importance of social determinants to low socio-economic populations., Conclusions: The survey revealed original standpoints and ideas towards willingness to promote targeted solutions. Healthcare leaders should consider and adapt local ideas to achieve effective planning following the insights of those working in the field., Discussion: Targeted conferences aimed at discussing health policy are an effective platform for presenting complex issues and for sharing ideas with colleagues for the benefit of meaningful long-term processes.

Introduction: The process of "informed consent" is currently being evaluated by the Ministry of Health, with the intent to recommend steps to improve patients' and doctors' satisfaction. Following the committee meetings, we decided to initiate an evaluation of the patient's perceptions regarding technical and logistic aspects of the process., Aims: To learn about patients' perceptions on the informed consent process, by evaluating different aspects and variables., Methods: One hundred patients who underwent an "informed consent" process, followed by general surgery, were interviewed using a formulated call-script. All the patients had surgery at Ramat Hayal Hospital during January 2020., Results: All the interviewed patients reported that their surgeon was the one who participated in the informed consent process. The majority of the patients (70%) reported that the meeting lasted between 10-20 minutes. Only 35% of the patients reported that the surgeon used auxiliary materials during the meeting. Almost all patients (96-99%) noted that the explanations delineated by the surgeon during their meeting were clear, satisfactory, and congruent with their real experiences of their surgery., Conclusions: Based on the results of this study, we confirm that the informed consent process for patients having surgery at the Ramat Hayal Hospital, is adequate and follows the recommendations of the law. Analyzing our data by the funding agent did not disclose meaningful differences except regarding the use of auxiliary materials. This issue will be examined in a future study., Discussion: These study results show a high compliance with the informed consent process in accordance with the law and MOH regulations.