The mouse HP1 proteins are essential for preventing liver tumorigenesis.

Chromatin organization is essential for appropriate interpretation of the genetic information. Here, we demonstrated that the chromatin-associated proteins HP1 are dispensable for hepatocytes survival but are essential within hepatocytes to prevent liver tumor development in mice with HP1ß being pivotal in these functions. Yet, we found that the loss of HP1 per se is not sufficient to induce cell transformation but renders cells more resistant to specific stress such as the expression of oncogenes and thus in fine, more prone to cell transformation. Molecular characterization of HP1-Triple KO premalignant livers and BMEL cells revealed that HP1 are essential for the maintenance of heterochromatin organization and for the regulation of specific genes with most of them having well characterized functions in liver functions and homeostasis. We further showed that some specific retrotransposons get reactivated upon loss of HP1, correlating with overexpression of genes in their neighborhood. Interestingly, we found that, although HP1-dependent genes are characterized by enrichment H3K9me3, this mark does not require HP1 for its maintenance and is not sufficient to maintain gene repression in absence of HP1. Finally, we demonstrated that the loss of TRIM28 association with HP1 recapitulated several phenotypes induced by the loss of HP1 including the reactivation of some retrotransposons and the increased incidence of liver cancer development. Altogether, our findings indicate that HP1 proteins act as guardians of liver homeostasis to prevent tumor development by modulating multiple chromatin-associated events within both the heterochromatic and euchromatic compartments, partly through regulation of the corepressor TRIM28 activity.

Antibiotic utilisation in adult and children patients in Kosovo hospitals.

OBJECTIVES: There are no reliable data on antibiotic use in Kosovo hospitals. The aim of this survey was to monitor volumes and patterns of antibiotic use in hospitalised patients in order to identify targets for quality improvement. METHODS: Data on antimicrobial use were collected from seven hospitals in Kosovo during 2013 using the standardised point prevalence survey (PPS) methodology as developed by the ESAC (European Surveillance of Antimicrobial Consumption) and ARPEC (Antibiotic Resistance and Prescribing in European Children). The survey included all inpatients receiving an antimicrobial agent on the day of the PPS. RESULTS: Overall, 1667 patients were included in the study: adults 1345 (81%) and children 322 (19%). Of the hospital inpatients, 579/1345 (43%) adults and 188/322 (58%) children received at least one antibiotic during a hospital stay. The top three antibacterial subgroups (ATC level 3) were ß-lactam antibiotics, cephalosporins and aminoglycosides. In all hospital centres, the most commonly prescribed antibiotic was ceftriaxone (39% for adult and 36% for children). Antibiotics were administered mainly parenterally in 74% of adults and 94% of children. Empirical prescribing was higher in adults 498/579 (86%) and children 181/188 (96%), compared with targeted treatment based on susceptibility testing-81 (14%) and 8 (4%), respectively. CONCLUSIONS: Antibiotic use in Kosovo's hospitals is very high. Gathered data will be an important tool to identify targets for quality improvement and will support preparation of guidelines and protocols for the prudent use of antibiotics.

Endoscopic Endonasal Surgery for Removal of Pituitary Adenomas: A Surgical Case Series of Treatment Results Using Different 2- and 3-Dimensional Visualization Systems.

BACKGROUND: Endoscopic endonasal transsphenoidal surgery (EETS) is a common treatment for patients with pituitary adenomas (PAs). A disadvantage of endoscopic surgery has been the lack of stereoscopic vision and depth perception. Recent developments offer high-definition 3-dimensional (3D-HD) visualization with a higher resolution and better image quality compared with 3D standard endoscopy (3D-SD). In this study, we compared treatment results of surgically treated patients with PAs using 3 different visualization systems: 2-dimensional (2D)-HD, 3D-SD, and 3D-HD. METHODS: Data from patients with primary PAs that were surgically treated between December 2008 and December 2017 were analyzed. Preoperative and postoperative tumor size and location, perioperative complications, and ophthalmologic, endocrine, and clinical outcomes were compared. RESULTS: A total of 170 patients underwent endoscopic resection of a primary PA (54 patients with 2D-HD, 75 with 3D-SD, and 41 with 3D-HD). Preoperatively, no statistical differences were found for tumor size, extension, and endocrine and ophthalmologic status. Tumor resection was not statistically different among the 3 groups. Complete resection was performed in 33 patients (80%) in the 3D-HD group, 54 patients (72%) in the 3D-SD group, and 39 patients (72%) in the 2D-HD group. The number of complications was not different across the groups (P = 0.436). Ophthalmologic outcomes did not differ based on EETS technique. The rate of new pituitary insufficiency was slightly lower in the 3D-HD group compared with 2D-HD and 3D-SD groups (4.8%, 16.6%, and 12%, respectively; P = 0.290). CONCLUSIONS: Although the resection rate was higher in the 3D-HD group, and subjective advantages of the 3D-HD endoscopes were noted, there were no significant differences in terms of gross total resection or new hormonal deficits among the 3 groups.