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, 6 h/d, 10 d), 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, 100 M) abolished cue-induced cocaine seeking on day 30, an effect that persisted 1 month, whereas the methyl donor S-adenosylmethionine (500 M) 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 (28 M) 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.

Objective To determine the impact of sleeve gastrectomy in patients suffering from depression compared with those who are not in a depressive state. Introduction Obesity is considered a global epidemic. Often patients with obesity suffer from depressive state. Depressive disorders may be both a cause and a consequence of obesity. Material and methods The study includes 300 consecutives patients that underwent laparoscopic sleeve gastrectomy. Out of the 300 patients, 253 (84.33%) of them completed the follow up for three years. Results Out of the 300-patients, with the average age of 41.65±11.05 years old, the ratio of males to females was 1:2. The average baseline BMI was 42.02 kg/m2. A total of 105 (35.33%) of the patients suffer from depression, which was more common in male (43%) than in female (31.5%), with statistically significant difference (p = .05). Comparing the weight loss after surgery in both groups, the mean weight loss in the depression-group was 12.0 ΔBMI and in the non-depression group was 13.03 ΔBMI, (p< .001). After three years, 94 (88.68%) patients of the depression group responded as they were optimistic and satisfied with the results of the operation, with positive changes in their lives, 8 (7.55%) did not experience change and 4 (3.77%) expressed to have worsened their depressive state. Conclusion Laparoscopic sleeve gastrectomy is successful and leads to weight loss even in subjects who are affected by depression syndrome.

Hernia through the obturator canal is usually unsuspected and hence undiagnosed. Patients with obturator hernias present as acute cases of intestinal obstruction secondary to strangulation or incarceration, with high rate of morbidity and mortality due to delayed diagnosis and treatment. The know incidence of obturator hernia is low, representing 0.073% (11 of 15,098) of all hernias repaired at the Mayo Clinic in a retrospective study of 15 years. In this study, we conducted a retrospective analysis of laparoscopic extraperitoneal hernia repairs that were performed between the years 2003 and 2007. All procedures were undertaken by 2 experienced surgeons who performed more than 150 previous surgeries. In 293 patients who underwent repair of bilateral or recurrent inguinal hernia, exploration of the obturator foramen was conducted looking for obturator hernia, which was found in 20 cases (6.82% of patients). The true incidence of obturator hernia is greater than that reported in the literature, and the chances of detecting hernia are greater if an equal number of men and women are scanned could be higher if pelvic scanning was performed.

Cue-induced cocaine craving intensifies, or 'incubates', during the first few weeks of abstinence and persists over extended periods of time. One important factor implicated in cocaine addiction is the endogenous opioid β-endorphin. In the present study, we examined the possible involvement of β-endorphin in the incubation of cocaine craving. Rats were trained to self-administer cocaine (0.75 mg/kg, 10 days, 6 h/day), followed by either a 1-day or a 30-day period of forced abstinence. Subsequent testing for cue-induced cocaine-seeking behavior (without cocaine reinforcement) was performed. Rats exposed to the drug-associated cue on day 1 of forced abstinence demonstrated minimal cue-induced cocaine-seeking behavior concurrently with a significant increase in β-endorphin release in the nucleus accumbens (NAc). Conversely, exposure to the cue on day 30 increased cocaine seeking, while β-endorphin levels remained unchanged. Intra-NAc infusion of an anti-β-endorphin antibody (4 μg) on day 1 increased cue-induced cocaine seeking, whereas infusion of a synthetic β-endorphin peptide (100 ng) on day 30 significantly decreased cue response. Both intra-NAc infusions of the δ opioid receptor antagonist naltrindole (1 μg) on day 1 and naltrindole together with β-endorphin on day 30 increased cue-induced cocaine-seeking behavior. Intra-NAc infusion of the μ opioid receptor antagonist CTAP (30 ng and 3 μg) had no behavioral effect. Altogether, these results demonstrate a novel role for β-endorphin and the δ opioid receptor in the development of the incubation of cocaine craving.

BackgroundHip fractures increase the risks of mortality and major morbidity in the elderly. Hip fractures are associated with chronic pain, reduced mobility, disability and increasing dependence. We evaluated the direct costs incurred to the Israeli healthcare system in 2013 as a result of hip fracture injuries in elderly patients.MethodsHip fractures costs evaluation consisted of first-year and long-term direct costs. Data on the incidence of hip fractures resulting in hospitalizations were retrieved from the Israeli Ministry of Health’s (MOH) Central Database of Hospital Admissions. Hospitalization, rehabilitation and nursing utilization rates and costs were estimated based on the professional literature and according to the MOH’s price list.ResultsDuring 2013, 6285 elderly patients were hospitalized in Israel due to hip fractures. Direct costs of hip fracture, comprising hospitalization, rehabilitation and nursing costs incurred during the first year after the injury, were estimated at 454 million New Israeli Shekels (NIS; 83,841 NIS per person). Long-term nursing care costs in 2013 were 265 million NIS, with an average cost of approximately 49,000 NIS for 1600 elderly persons receiving long-term nursing care as a result of a hip fracture. Overall, the total direct costs of hip fracture in the elderly population in Israel in 2013 were 719 million NIS.ConclusionsThe direct costs of hip fractures in Israel among the elderly are approximately 719 million NIS per year. The majority of costs are associated with the first year following the injury. To reduce healthcare costs in Israel, changes in the country’s healthcare policy on hip fractures are required. For example, there is a need for a program for detecting high- risk populations, and for early intervention following the injury.Electronic supplementary materialThe online version of this article (10.1186/s13584-018-0235-y) contains supplementary material, which is available to authorized users.