1. |
- Hansson, Gert-Åke, et al.
(författare)
-
Questionnaire versus direct technical measurements in assessing postures and movements of the head, upper back, arms and hands
- 2001
-
Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 27:1, s. 30-40
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study compares questionnaire-assessed exposure data on work postures and movements with direct technical measurements. METHODS: Inclinometers and goniometers were used to make full workday measurements of 41 office workers and 41 cleaners, stratified for such factors as musculoskeletal complaints. The subjects answered a questionnaire on work postures of the head, back, and upper arms and repeated movements of the arms and hands (3-point scales). The questionnaire had been developed on the basis of a previously validated one. For assessing worktasks and their durations, the subjects kept a 2-week worktask diary. Job exposure was individually calculated by time-weighting the task exposure measurements according to the diary. RESULTS: The agreement between the self-assessed and measured postures and movements was low (kappa = 0.06 for the mean within the occupational groups and kappa = 0.27 for the whole group). Cleaners had a higher measured workload than office workers giving the same questionnaire response. Moreover, the subjects with neck-shoulder complaints rated their exposure to movements as higher than those without complaints but with the same measured mechanical exposure. In addition, these subjects also showed a general tendency to rate their postural exposure as higher. The women rated their exposure higher than the men did. CONCLUSIONS: The questionnaire-assessed exposure data had low validity. For the various response categories the measured exposure depended on occupation. Furthermore, there was a differential misclassification due to musculoskeletal complaints and gender. Thus it seems difficult to construct valid questionnaires on mechanical exposure for establishing generic exposure-response relations in epidemiologic studies, especially cross-sectional ones. Direct technical measurements may be preferable.
|
|
2. |
- Mohell, N., et al.
(författare)
-
APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cells
- 2015
-
Ingår i: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Two main causes of platinum resistance are mutation in the tumor suppressor gene TP53 and drug-induced increase in intracellular glutathione concentration. Mutations in TP53 occur in about 50% of human tumors. APR-246 (PRIMA-1(MET)) is the first clinical-stage compound that reactivates mutant p53 and induces apoptosis. APR-246 is a prodrug that is converted to the active compound methylene quinuclidinone (MQ), a Michael acceptor that binds to cysteine residues in mutant p53 and restores its wildtype conformation. Here, we show that MQ also binds to cysteine in glutathione, thus decreasing intracellular free glutathione concentration. We also show that treatment with APR-246 completely restores the cisplatin and doxorubicin sensitivity to p53-mutant drug-resistant ovarian cancer cells. We propose that this unique ability of APR-246/MQ to bind to cysteines in both mutant p53 and glutathione has a key role in the resensitization as well as in the outstanding synergistic effects observed with APR-246 in combination with platinum compounds in ovarian cancer cell lines and primary cancer cells. However, MQ binding to cysteines in other targets, for example, thioredoxin reductase, may contribute as well. Strong synergy was also observed with the DNA-damaging drugs doxorubicin and gemcitabine, while additive effects were found with the taxane docetaxel. Our results provide a strong rationale for the ongoing clinical study with APR-246 in combination with platinum-based therapy in patients with p53-mutant recurrent high-grade serous (HGS) ovarian cancer. More than 96% of these patients carry TP53 mutations. Combined treatment with APR-246 and platinum or other DNA-damaging drugs could allow dramatically improved therapy of a wide range of therapy refractory p53 mutant tumors.
|
|
3. |
|
|
4. |
|
|
5. |
- Nordander, Catarina, et al.
(författare)
-
Muscular rest and gap frequency as EMG measures of physical exposure: the impact of work tasks and individual related factors
- 2000
-
Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 43:11, s. 1904-1919
-
Tidskriftsartikel (refereegranskat)abstract
- Owing to an orderly recruitment of motor units, low threshold type I fibres are presumed to be vulnerable in contractions of long duration. To study load on these fibres muscular rest was registered as the time fraction of electromyographic (EMG) activity below a threshold. Moreover, the frequency of periods with muscular rest, EMG gaps, was derived, since a low gap frequency has been shown to be a risk factor for musculoskeletal disorders. Trapezius EMG was registered in 24 female hospital cleaners, 21 female office workers and 13 male office workers during one working day. Cleaners have a high risk of neck/shoulder pain and had much less muscular rest than office workers measured as a percentage of total registered time (median value = 1.5%, range = 0.2-13% vs. median value = 12%, range = 0.0-32%, respectively). Gap frequency showed no difference between the two occupational groups. Both measures displayed a wide inter-individual variation. For the cleaners, some of the variance was explained by body mass index (BMI) and age, with lower values of muscular rest for older subjects with a high BMI. Among the office workers, low values of muscular rest and a high gap frequency were registered in subjects with a low subjective muscular tension tendency. Gender, strength, smoking, job strain, employment time and musculoskeletal symptoms had no impact on either EMG measure.
|
|