This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with "temperament," including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/ bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor. addiction | dopamine | fibroblast growth factor | nucleus accumbens | reinstatement A pproximately 16% of adults in the United States report drug use within the past year (1). However, not everyone who experiments with drugs becomes an addict, as an estimated 8.5% of the population, or 25 million Americans, meet Diagnostic and Statistical Manual of Mental Disorders IV (2) criteria for substance abuse and dependence (1). Environmental and societal factors play a role in addiction liability (e.g., refs. 3-5), and there is ample evidence demonstrating a role for genetic factors (e.g., refs. 6-10). However, studying the interplay among these factors is difficult in human studies because of the inability to control for environmental factors and the challenge of parsing causes from consequences. Preclinical animal models are therefore essential for defining the complex interactions between genes and environment, and uncovering the neural mechanisms that might render an individual more susceptible to drug addiction. The first animal model characterizing individual differences in the propensity to take drugs of abuse was introduced over two decades ago by Piazza et al. (11), who showed that, like humans, only some rats readily self-administer such drugs. Furthermore...

BackgroundIntroducing patient safety and quality improvement science to medical students is integral to improving healthcare. However, developing and implementing a patient safety curriculum can be challenging in a medical school curriculum that is already densely packed. Our aim was to develop and evaluate the impact of a workshop introducing patient safety and quality improvement science to a large class of first-year medical students.MethodAs a part of an evolving longitudinal patient safety curriculum, an introductory workshop on patient safety was integrated into an anatomy course. A high impact event (a simulated “retained sponge” discovery during an anatomy dissection lab) was used to introduce medical error. The educational session which followed consisted of a presentation by an interprofessional team utilizing the retained sponge as example of an error. Use of safety tools was introduced and quality improvement science was discussed using the evolution of methods to decrease retained foreign objects during surgery. A patient’s story told by a close family member about the personal impact of medical errors was presented. Students then participated in an interactive breakout activity and completed a module on safety. The impact of the workshop was assessed through pre- and post- session tests.ResultsQuantitative and qualitative evaluation reflected a positive effect of the session in improving students’ safety knowledge and attitudes. Students’ mean total knowledge improved from 7.58 to 8.98 (p = 0.000). Mean total attitudes score improved from 47.73 to 50.56 (p = 0.000). Students’ comments after the workshop reflected increased awareness and appreciation of the importance of addressing medical errors.ConclusionA workshop introducing patient safety and quality improvement to first year medical students improved knowledge and attitudes regarding safety and increased awareness of the importance of addressing medical errors in their future careers. Integrating patient safety education into an existing foundational science course is a model for teaching patient safety at other medical schools.

Study Objective: Operative hysteroscopy requires elevated intrauterine pressures, which could lead to the spread of malignant cells into the peritoneal cavity. Currently, there is a paucity of data analyzing clinical outcomes in endometrial cancer after hysteroscopic morcellation with newer equipment. In this study, we sought to determine whether there are increased rates of positive peritoneal cytology, lymphovascular space invasion, or surgical upstaging in patients undergoing hysteroscopic morcellation compared with alternative endometrial biopsy methods. Design: A retrospective chart review of patients from 2013−2018 was performed. The exclusion criteria included biopsy at outside institution, stage IV endometrial cancer known before biopsy, and missing data regarding biopsy method and histology. Peritoneal cytology results, lymphovascular space invasion, and surgical staging were compared by method of biopsy and histology using chi-square and Kruskal-Wallis tests. Setting: The patients included in this study were accrued from the Karmanos Cancer Insittute in Detroit, Michigan. Patients: A total of 289 patients met the inclusion criteria: 184 patients were classified as low-grade (F ed eration Internationale de Gyn ecologie et d'Obst etrique grades 1 and 2) and 105 as high-grade (F ed eration Internationale de Gyn ecologie et d'Obst etrique grade 3, serous, clear cell, and carcinosarcoma) endometrial cancer. Interventions: Fifty-three patients (18%) underwent hysteroscopy with morcellation. Alternative biopsy methods included hysteroscopy without morcellation, n = 81 (28%); endometrial biopsy, n = 112 (38.7%); and dilation and curettage, n = 43 (15%). Measurements and Main Results: Positive peritoneal cytology was noted in 34 cases (12%) and negative cytology in 165 (57%). Cytology was not performed in 90 cases (31%). When comparing outcomes by histologic subtypes, no difference was seen in peritoneal cytology (p = .704 and .727 for low grade and high grade, respectively), stage (p = .773 and .053 for low grade and high grade, respectively) or lymphovascular space invasion (p = .400 and .142 for low grade and high grade, respectively). Conclusion:Our study demonstrates that hysteroscopy with morcellation is a safe diagnostic method for low-and highgrade endometrial pathologic conditions and does not lead to increased dissemination of malignant cells, lymphovascular space invasion, or upstaging of patients.

Patients with comorbid lichen sclerosus and high-grade squamous intraepithelial lesion treated with topical corticosteroids do not have an increased risk of high-grade squamous intraepithelial lesion recurrence.

No abstract