Synthesis and molecular modelling of unsaturated exomethylene pyranonucleoside analogues with antitumor and antiviral activities

This report describes the total and facile synthesis of the unsaturated keto and exomethylene pyranonucleoside analogues, 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10), 1-(2,3-dideoxy-alpha-D-glycero-hex-2-enopyranosyl-4-ulose)uracil (17) and 1-(2,3,4-trideoxy-4-methylene-alpha-D-glycero-hex-2-enopyranosyl)uracil (18). Commercially available 1,2,3,4,6-penta-O-acetyl-alpha-D-mannopyranose (1) was condensed with silylated uracil, deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-alpha-D-mannopyranosyl)uracil (4). Two different synthetic routes were investigated for the conversion of 4 into the olefinic derivative 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10). Although the two procedures are quite similar with respect to yields and final products, the second also leads to the keto-2',3'-unsaturated analogue (17). The new analogues were evaluated for their anticancer and antiviral activities using several tumor cell lines and gastrointestinal rotavirus. All of the compounds showed direct antiviral effect against rotavirus infectivity in Caco-2 cell line. Moreover, 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10) was found to be potent in MCF-7 breast carcinoma cell line.     

A diary study to open up the black box of overtime work among university faculty members

OBJECTIVES: This study aimed at opening up the black box of overtime work among university faculty members by providing information on (i) when faculty members work overtime, (ii) what activities are undertaken during overtime, and (iii) how overtime is experienced. METHODS: Data were collected among 120 Dutch faculty members who completed a general questionnaire (addressing general overtime hours, work characteristics, and well-being) and a 9-day diary study (with information on daily overtime hours, activities, and experiences). Analyses of variance were used to analyze the data. RESULTS: Overtime was very prevalent among faculty members, high overtime workers being nonfatigued, engaged employees with positive work characteristics. Overtime was unevenly distributed over the week, being common on Sunday and Monday and uncommon on Friday and Saturday. Overtime activities during the weekend differed from those during the workweek, relatively much time being spent on research during weekend overtime. Overtime activities were experienced differently than activities during regular hours, overtime work being experienced as less effortful and less stressful than regular workhours and weekend overtime being less pleasurable than regular hours and evening overtime. CONCLUSIONS: This detailed day-to-day mapping and evaluation of overtime work contributes to a better understanding of overtime work by demonstrating meaningful patterns of overtime over the (work)week and meaningful associations between overtime activities and time-contingent experiences. It is suggested that worktime control plays an important role in explaining the results.     

First clinical experience of argon neutral plasma energy in gynaecological surgery in the UK

We describe the first in vivo use of neutral argon plasma energy in gynaecological surgery in the UK and the largest series worldwide. The use of PlasmaJet® (PJ) in different applications in 118 selected cases in a tertiary referral centre for gynaecological oncology and minimal access surgery was assessed. The effectiveness, ease of use, ergonomics and safety of PJ in gynaecological surgery is evaluated prospectively. Following this experience, we have devised a table of recommended power settings for different applications.     

The role of motivation in distracting attention away from pain: An experimental study

Research on the effectiveness of distraction as a method of pain control is inconclusive. One mechanism pertains to the motivational relevance of distraction tasks. In this study the motivation to engage in a distraction task during pain was experimentally manipulated. Undergraduate students (N = 73) participated in a cold pressor test (CPT) and were randomly assigned to three groups: a distraction-only group performed a tone-detection task during the CPT, a motivated-distraction group performed the same task and received a monetary reward for good task performance, and a control group did not perform the tone-detection task. Results indicated that engagement in the distraction task was better in the motivated-distraction group in comparison with the distraction-only group. Participants in both distraction groups experienced less pain compared to the control group. There were no overall differences in pain intensity between the two distraction groups. The effect of distraction was influenced by the level of catastrophic thinking about pain. For low catastrophizers, both distraction groups reported less pain as compared to the non-distracted control group. This was not the case for high catastrophizers. For high catastrophizers it mattered whether the distraction task was motivationally relevant: high catastrophizers reported less intense pain in the motivated-distraction group, as compared to the non-distracted control group. We conclude that increasing the motivational relevance of the distraction task may increase the effects of distraction, especially for those who catastrophize about pain.