A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF.

Objectives: The purpose of this study was to test the feasibility of a sexual abuse prevention education in a sample of Chinese preschool children in Beijing, China. Method: One hundred and fifty preschool children were randomly assigned to either the intervention group (N ¼ 78) or the wait-list control group (N ¼ 72). Children were posttested on sexual abuse prevention knowledge and self-protection skills gains. Results: Following program participation, preschool children in the intervention group demonstrated greater knowledge about sexual abuse prevention and higher levels of self-protection skills compared with children in the wait-list control group. Conclusions: Findings suggest that it is feasible to implement the sexual abuse prevention education with Chinese preschoolers. Applications and limitations of these findings are discussed.

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BackgroundTissue adhesive injection is the first‐line treatment for gastric varices rebleeding. Available studies are focused on antibiotic usage in emergency endoscopy, while the use of antibiotics in selective endoscopic tissue adhesive treatment remains controversial.MethodsThis is a randomized controlled study conducted in a tertiary referral hospital. Consecutive patients were enrolled from February 16, 2016, to November 19, 2016, and blindly randomized into two treatment groups. Patients in the prophylactic group received 2 g of cefotiam during endoscopic injection of tissue adhesive. All the subjects were observed for rebleeding, fever, and changes in laboratory indicators in hospital and post‐discharge.ResultOne hundred and seven patients who received endoscopic therapy for gastroesophageal varices were included. Fifty‐three patients were allocated to the antibiotic prophylactic group and 54 patients to the on‐demand group. The two groups had similar baseline characteristics. The incidence of fever in hospital was 2/53 (3.8%) vs 9/54 (16.7%) (P = 0.028). Perioperative and postoperative clinical events were significantly lower in the antibiotic prophylactic group (5.7% vs 24.1%, P = 0.018; 7.5% vs 20.4%, P = 0.050). Inflammation indices were elevated on the first day after endoscopic therapy; however, no significant difference was observed between the two groups. The cumulative rebleeding free rate within 2 months was lower in the antibiotic prophylactic group (1.9% vs 9.3%, P = 0.100).ConclusionOur study illustrated that prophylactic use of antibiotics in selective endoscopic injection of tissue adhesive reduced the incidence of the total clinical events in perioperative period and had a trend towards lower rebleeding in 2 months.

While midbrain dopamine (DA) neuronal circuits are central to motivated behaviors, much remains unknown about our knowledge of how these circuits are modified over time by experience to facilitate selective aspects of experience-dependent plasticity. Most studies of the DA system in drug addiction focus on the role of the mesolimbic DA pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) in facilitating drug-associated reward. In contrast, less is known about how midbrain DA cells and associated circuits contribute to negative affective states including anxiety that emerge during protracted withdrawal from drug administration. Here, we demonstrate the selective role of a midbrain DA projection to the amygdala (VTADA→Amygdala) for anxiety that develops during protracted withdrawal from cocaine administration but does not participate in cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach revealed a persistent elevation in spontaneous and task-related activity of GABAergic cells from the bed nucleus of the stria terminals (BNST) and downstream VTADA→Amygdala cells that could be detected even after a single cocaine exposure. Activity in BNSTGABA cells was related to cocaine-induced anxiety but not reward or sensitization, and silencing the projection from these cells to the midbrain was sufficient to prevent the development of anxiety during protracted withdrawal following cocaine administration. We observed that VTADA→Amygdala cells, but not other midbrain DA cells, were strongly activated after a challenge exposure to cocaine, and found that activity in these cells was necessary for the expression of reinstatement of cocaine place preference. Lastly, the importance of activity in VTADA→Amygdala cells extends beyond cocaine, as these cells mediate the development of anxiety states triggered by morphine and a predator odor. Our results provide an exemplar for how to identify key circuit substrates that contribute to behavioral adaptations and reveal a critical role for BNSTGABA→VTADA→Amygdala pathway in anxiety states induced by drugs of abuse or natural experiences as well as cocaine-primed reinstatement of conditioned place preference.

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