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| 2. |
- Hay, Sam, et al.
(författare)
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Moving a phenol hydroxyl group from the surface to the interior of a protein : effects on the phenol potential and pK(A).
- 2005
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Ingår i: Biochemistry. - 0006-2960. ; 44:35, s. 11891-902
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Tidskriftsartikel (refereegranskat)abstract
- De novo protein design and electrochemistry were used to measure changes in the potential and pK(A) of a phenol when its OH group is moved from a solvent-exposed to a sequestered protein position. A "phenol rotation strategy" was adopted in which phenols, containing a SH in position 4, 3, or 2 relative to the OH group, were bound to a buried protein site. The alpha(3)C protein used here is a tryptophan to cysteine variant of the structurally defined alpha(3)W protein (Dai et al. (2002) J. Am. Chem. Soc. 124, 10952-10953). The protein characteristics of alpha(3)C and the three mercaptophenol-alpha(3)C (MP-alpha(3)C) proteins are shown to be close to those of alpha(3)W. Moreover, the phenol OH group is fully solvent exposed in 4MP-alpha(3)C and more sequestered in 3MP-alpha(3)C and 2MP-alpha(3)C. Here we compare the redox properties of the three mercaptophenols when bound to alpha(3)C and to cysteine free in water. The pK(A) and E(peak) values are essential identical when 4MP is ligated to alpha(3)C relative to when it is free in solution. In contrast, these values are increased in 3MP-alpha(3)C and 2MP-alpha(3)C relative to the solvated compounds. The E(peak) vs pH plots all display a approximately 59 mV/pH unit dependence. We conclude that interactions with the OH group dominate the phenol redox characteristics. In 3MP-alpha(3)C and 2MP-alpha(3)C, hydrogen bonds between the protein and the bound phenols appear to either stabilize the reduced phenol or destabilize the radical, relative to the aqueous buffer, raising the potential by 0.11 and 0.12 V, respectively.
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| 3. |
- Hay, Sam, et al.
(författare)
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Redox characteristics of a de novo quinone protein.
- 2007
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Ingår i: J Phys Chem B. - 1520-6106. ; 111:13, s. 3488-95
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Tidskriftsartikel (refereegranskat)abstract
- The electrochemistry of 2,6-dimethylbenzoquinone (DMBQ) has been characterized for three different systems: DMBQ freely solvated in aqueous buffer; DMBQ bound to a neutral, blocked cysteine (N-acetyl-L-cysteine methyl ester) and the resulting DMBQ-bCys compound solvated in aqueous buffer; and DMBQ bound to a small model protein denoted alpha(3)C. The goal of this study is to detect and characterize differences in the redox properties of the protein-ligated DMBQ relative to the solvated quinones. The alpha(3)C protein used here is a tryptophan-32 to cysteine-32 variant of the structurally defined alpha(3)W de novo protein (Dai et al. J. Am. Chem. Soc. 2002, 124, 10952-10953). The properties of alpha(3)C were recently described (Hay et al. Biochemistry 2005, 44, 11891-11902). DMBQ was covalently bound to bCys and alpha(3)C through a sulfur substitution reaction with the cysteine thiol. In contrast to the solvated DMBQ and DMBQ-bCys compounds, diffusion controlled electrochemistry of DMBQ-alpha(3)C showed well-behaved and fully reversible n = 2 oxidation/reduction with a peak separation of approximately 30 mV between pH 5 and 9. DMBQ-alpha(3)C could also be immobilized on a gold electrode modified with a self-assembled monolayer of 3-mercaptopropionoic acid, allowing the measurement, by cyclic voltammetry, of an apparent rate of electron transfer of 22 s(-1). The (cysteine) sulfur substitution significantly lowers one of the hydroquinone pKA's from 10.4 in DMBQ to 6.8 in DMBQ-bCys. This pKA is slightly elevated in DMBQ-alpha(3)C to 7.0 and the E1/2 at pH 7.0 is raised by 110 mV from +190 mV in DMBQ-bCys to +297 mV in DMBQ-alpha(3)C.
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| 5. |
- Head, Jenny, et al.
(författare)
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Diagnosis-specific sickness absence as a predictor of mortality : the Whitehall II prospective cohort study.
- 2008
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1468-5833 .- 0959-8138 .- 1756-1833. ; 337, s. a1469-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether knowing the diagnosis for sickness absence improves prediction of mortality. DESIGN: Prospective cohort study established in 1985-8. Sickness absence records including diagnoses were obtained from computerised registers. SETTING: 20 civil service departments in London. PARTICIPANTS: 6478 civil servants aged 35-55 years. MAIN OUTCOME MEASURES: All cause, cardiovascular, and cancer mortality until 2004, average follow-up 13 years. RESULTS: After adjustment for age, sex, and employment grade, employees who had one or more medically certified spells of sickness absence (>7 days) in a three year period had a mortality 1.7 (95% CI 1.3 to 2.1) times greater than those with no medically certified spells. Inclusion of diagnoses improved the prediction of all cause mortality (P=0.03). The hazard ratio for mortality was 4.7 (2.6 to 8.5) for absences with circulatory disease diagnoses, 2.2 (1.4 to 3.3) for surgical operations, and 1.9 (1.2 to 3.1) for psychiatric diagnoses. Psychiatric absences were also predictive of cancer mortality (2.5 (1.3 to 4.7)). Associations of infectious, respiratory, and injury absences with overall mortality were less marked (hazard ratios from 1.5 to 1.7), and there was no association between musculoskeletal absences and mortality. CONCLUSIONS: Major diagnoses for medically certified absences were associated with increased mortality, with the exception of musculoskeletal disease. Data on sickness absence diagnoses may provide useful information to identify groups with increased health risk and a need for targeted interventions.
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| 6. |
- Kivimäki, Mika, et al.
(författare)
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Diagnosis-specific sick leave as a risk marker for disability pension in a Swedish population.
- 2007
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Ingår i: J Epidemiol Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 61:10, s. 915-20
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diagnosis-specific sick leave as a risk marker for disability pension in a Swedish population.Kivimäki M, Ferrie JE, Hagberg J, Head J, Westerlund H, Vahtera J, Alexanderson K.Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK. m.kivimaki@ucl.ac.ukOBJECTIVE: To investigate diagnosis-specific sick leave as a risk marker for subsequent disability pension. DESIGN: A prospective population based cohort study. Exposure to a new medically certified sick leave episode of more than seven days by diagnosis during 1985 was examined in relation to incident cause-specific disability pension through 1996. PARTICIPANTS: The total non-retired population of one Swedish county aged 16 to 49 years, alive and not in receipt of a disability pension at the end of 1985 (176 629 persons; 51% men). MAIN RESULTS: To eliminate confounding by sick leaves that translate into a disability pension, the follow up period for disability pension was started five years after the assessment of sick leave. After adjustment for demographic characteristics, the risk of disability pension from mental disorders was 14.1 times higher (95% confidence interval (CI), 12.1 to 16.4) for those with sick leave for mental disorders than for those with no sick leave. The corresponding hazard ratio for sick leave and disability pension within diagnostic category was 5.7 (95% CI, 5.3 to 6.2) for musculoskeletal diseases and 13.0 (7.7 to 21.8) for gastrointestinal diseases. Irrespective of diagnoses, the hazard ratio for sick leave and disability pension was 3.0 (2.9 to 3.1). CONCLUSIONS: Sick leave may provide an important risk marker for identifying groups at high risk of a disability pension, especially for psychiatric diagnoses.
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| 7. |
- Melchior, Maria, et al.
(författare)
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Using sickness absence records to predict future depression in a working population : prospective findings from the GAZEL cohort.
- 2009
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Ingår i: American journal of public health. - 1541-0048. ; 99:8, s. 1417-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We tested the hypothesis that sickness absence from work predicts workers' risk of later depression. METHODS: Study participants (n = 7391) belonged to the French GAZEL cohort of employees of the national gas and electricity company. Sickness absence data (1996-1999) were obtained from company records. Participants' depression in 1996 and 1999 was assessed with the Center for Epidemiologic Studies-Depression (CES-D) scale. The analyses were controlled for baseline age, gender, marital status, occupational grade, tobacco smoking status, alcohol consumption, subthreshold depressive symptoms, and work stress. RESULTS: Among workers who were free of depression in 1996, 13% had depression in 1999. Compared with workers with no sickness absence during the study period, those with sickness absence were more likely to be depressed at follow-up (for 1 period of sickness absence, fully adjusted odds ratio [OR] = 1.53, 95% confidence interval [CI] = 1.28, 1.82; for 2 or more periods, fully adjusted OR = 1.95, 95% CI = 1.61, 2.36). Future depression was predicted both by psychiatric and nonpsychiatric sickness absence (fully adjusted OR = 3.79 [95% CI = 2.81, 5.10] and 1.41 [95% CI = 1.21, 1.65], respectively). CONCLUSIONS: Sickness absence records may help identify workers vulnerable to future depression.
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| 8. |
- Myrvold, Kristina, et al.
(författare)
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Sikhism
- 2008
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Ingår i: Religion i Sverige. - 9789175041995 ; , s. 289-293
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Bokkapitel (refereegranskat)
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| 9. |
- Westerlund, Hugo, et al.
(författare)
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Work-related sleep disturbances and sickness absence in the Swedish working population, 1993-1999.
- 2008
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Ingår i: Sleep. - 0161-8105. ; 31:8, s. 1169-77
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Tidskriftsartikel (refereegranskat)abstract
- Work-related sleep disturbances and sickness absence in the Swedish working population, 1993-1999.Westerlund H, Alexanderson K, Akerstedt T, Hanson LM, Theorell T, Kivimäki M.Stress Research Institute, Stockholm University, Stockholm, Sweden. hugo.westerlund@stressforskning.su.seSTUDY OBJECTIVES: To examine secular trends in work-related sleep disturbances and their association with sickness absence in the Swedish working population. DESIGN: Nationally representative cross-sectional samples of the Swedish working population aged 16-64 (the biennial Swedish Work Environment Survey) in 1993, 1995, and 1999 respectively. Questionnaire data on work-related sleep disturbances were linked to records of medically-certified sick-leave spells exceeding 14 days obtained from national registers. SETTING: All Sweden. PARTICIPANTS: A total of 28,424 individuals aged 16-65 with complete data (5162/5173 women/men in 1993; 4635/4764 in 1995; and 4422/4268 in 1999). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The age-adjusted proportion of women with work-related sleep disturbances at least once a week increased from 12.3% in 1993 to 21.7% in 1999 (P < 0.001). The corresponding figures for men were 12.5% to 18.6% (P < 0.001). There was a strong cross-sectional association between work-related sleep disturbances and sickness absence in both genders and in each studied year. Using binary logistic regressions and adjusting for age, supervisory position, and geographical region, the odds ratios for sickness absence for those who reported work-related sleep disturbances every day, compared with those who answered "not at all/seldom last 3 months" varied between 3.22 (1.88-5.50) and 4.26 (2.56-7.19), with the strongest associations seen in 1999. Adjustment for health indicators, especially depressive symptoms, attenuated the relationship substantially. CONCLUSIONS: Self-reported sleep disturbances attributed to work-related causes were on the rise in Sweden and were associated with medically-certified sickness absence. Most of this association seems to be accounted for by depressive symptoms.
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