Reactions of isolated rat aorta to X-irradiation

The reaction of isolated helical strips of rat aorta to X-irradiation was studied: X-rays (50 kV) induced a reproducible, reversible contractile response at threshold doses of 2.5 Gy (60 Gy/min) and 10 Gy (30 Gy/min). After repeated irradiation with the same doses at equal time intervals and constant dose-rate (for example 50 Gy every 15 min, dose-rate 60 Gy/min) the contractile response was progressively diminished, i.e. a tachyphylaxis appeared. The preparations still reacted even after total doses over 1000 Gy. The X-ray induced contractile responses were dose- and dose-rate dependent. Quantitative analysis indicated no essential differences in the radiation-induced contractile response when recorded under isometric or isotonic conditions. After hypothermia (20 degrees C) or hyperthermia (42 degrees C) no visible radiation response could be induced. Part of the aortic strips were spontaneously active: X-ray doses of 5 to 10 Gy stimulated, while doses of 100 to 200 Gy inhibited or blocked the spontaneous phasic activity. A comparison between the immediate X-ray reaction of vascular and non-vascular smooth muscle preparations is given. Participation of cholinergic and adrenergic mechanisms in the X-ray induced contractions of rat aorta seems to be ruled out, because the blocking agents atropine, phentolamine, and bretylium had no effect.     

Preforming of polydioxanone sheets for orbital wall fractures – A technical note

Introduction

Polydioxanone (PDS) sheets are commonly used in the treatment of orbital wall fractures. A potential drawback of PDS is that it may be difficult to adapt to the anatomy of the orbital walls. Therefore a study was conceived to test the feasibility of preforming PDS sheets.

Performance Evaluations of a Novel Continuous Glucose Monitor: Evaluation of the Performance of a Novel System for Continuous Glucose Monitoring

Background

The performance of a continuous glucose monitoring (CGM) system in the early stage of development was assessed in an inpatient setting that simulates daily life conditions of people with diabetes. Performance was evaluated at low glycemic, euglycemic, and high glycemic ranges as well as during phases with rapid glucose excursions.

Methods

Each of the 30 participants with type 1 diabetes (15 female, age 47 ± 12 years, hemoglobin A1c 7.7% ± 1.3%) wore two sensors of the prototype system in parallel for 7 days. Capillary blood samples were measured at least 16 times per day (at least 15 times per daytime and at least once per night). On two subsequent study days, glucose excursions were induced. For performance evaluation, the mean absolute relative difference (MARD) between CGM readings and paired capillary blood glucose readings and precision absolute relative difference (PARD), i.e., differences between paired CGM readings were calculated.

Results

Overall aggregated MARD was 9.2% and overall aggregated PARD was 7.5%. During induced glucose excursions, MARD was 10.9% and PARD was 7.8%. Lowest MARD (8.5%) and lowest PARD (6.4%) were observed in the high glycemic range (euglycemic range, MARD 9.1% and PARD 7.4%; low glycemic range, MARD 12.3% and PARD 12.4%).

Conclusion

The performance of this prototype CGM system was, particularly in the hypoglycemic range and during phases with rapid glucose fluctuations, better than performance data reported for other commercially available systems. In addition, performance of this prototype sensor was noticeably constant over the whole study period. This prototype system is not yet approved, and performance of this CGM system needs to be further assessed in clinical studies.     

From the Cover: Trim24 targets endogenous p53 for degradation

Numerous studies focus on the tumor suppressor p53 as a protector of genomic stability, mediator of cell cycle arrest and apoptosis, and target of mutation in 50% of all human cancers. The vast majority of information on p53, its protein-interaction partners and regulation, comes from studies of tumor-derived, cultured cells where p53 and its regulatory controls may be mutated or dysfunctional. To address regulation of endogenous p53 in normal cells, we created a mouse and stem cell model by knock-in (KI) of a tandem-affinity-purification (TAP) epitope at the endogenous Trp-53 locus. Mass spectrometry of TAP-purified p53-complexes from embryonic stem cells revealed Tripartite-motif protein 24 (Trim24), a previously unknown partner of p53. Mutation of TRIM24 homolog, bonus, in Drosophila led to apoptosis, which could be rescued by p53-depletion. These in vivo analyses establish TRIM24/bonus as a pathway that negatively regulates p53 in Drosophila. The Trim24-p53 link is evolutionarily conserved, as TRIM24 depletion in human breast cancer cells caused p53-dependent, spontaneous apoptosis. We found that Trim24 ubiquitylates and negatively regulates p53 levels, suggesting Trim24 as a therapeutic target to restore tumor suppression by p53.     

Epicoccamides B-D, glycosylated tetramic acid derivatives from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa

Three new tetramic acid derivatives, epicoccamides B-D, together with the known epicoccamide, were isolated from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa. The structures of the new compounds were elucidated on the basis of their physical data and chemical degradation. The epicoccamides differ in substitution pattern and in the size of the central carbon chain. The derivative with the longest chain, epicoccamide D, induces morphogenesis and pigment formation in surface cultures of the fungus Phoma destructiva at a concentration of 1.7 mM. Moreover, it exhibits weak to moderate cytotoxicity to HeLa cell lines (CC50 17.0 microM) and antiproliferative effects toward mouse fibroplast (L-929) and human leukemia cell lines (K-562) with growth inhibition (GI50) of 50.5 and 33.3 microM, respectively.     

Work-related factors and violence among nursing staff in the European NEXT study: a longitudinal cohort study

BACKGROUND: The occurrence of workplace violence is rather frequent within the nursing profession, with well-known consequences on the psychological health of victims. OBJECTIVES: This study is aimed at assessing the relationships between relevant individual, organizational, and psychosocial factors, and the frequency of several types of workplace violence; the direct as well as the interactive impact of violence and psychosocial factors on organizational commitment and perceived health. DESIGN: Questionnaire-based cross-sectional and longitudinal survey designs were employed for the two study objectives, respectively. SETTING: Five hundred and sixty-five healthcare institutions from eight European countries participated in the Nurses' Early Exit Study. PARTICIPANTS: The 34,107 participants were nursing staff holding different qualifications. The response rate was 55.1% in the cross-sectional part and 40.5% in the follow-up phase. At baseline, the respondents were mostly female (89.3%), in the age group 30-44 years (52.9%), registered or specialized nurses (67.0%), working mainly in medico-surgical wards (36.3%), and employed full-time (72.8%). METHODS: In the cross-sectional analysis, the relationship between the predictor variables and frequency of violence was assessed by means of a hierarchical multiple linear regression. In the longitudinal analysis, main direct and interactive effects of violence and psychosocial factors on perceived health and organizational commitment were assessed by means of hierarchical multiple linear regression analyses with interaction terms. RESULTS: Higher levels of adverse work-related factors were significantly associated with higher frequency of the distinguished types of violence. Significant interactions were found between psychosocial factors and violence only in predicting organizational commitment, even if effect sizes were very low. No interactions were observed for perceived health. The prevalence of the distinguished types of violence varied across the participating countries according to the presence of adverse work- and non-work-related factors. CONCLUSIONS: These findings suggest the necessity of interventions both over working conditions conducive to violence and violent behaviours themselves.