| 1. |
- Asp, Vendela, et al.
(författare)
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Chiral effects in adrenocorticolytic action of o,p'-DDD (mitotane) in human adrenal cells
- 2010
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Ingår i: Xenobiotica. - : Informa UK Limited. - 0049-8254 .- 1366-5928. ; 40:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- 1. Adrenocortical carcinoma (ACC) is a rare malignant disease with poor prognosis. The main pharmacological choice, o,p'-DDD (mitotane), produces severe adverse effects. 2. Since o,p'-DDD is a chiral molecule and stereoisomers frequently possess different pharmacokinetic and/or pharmacodynamic properties, we isolated the two o,p'-DDD enantiomers, (R)-(+)-o,p'-DDD and (S)-(-)-o,p'-DDD, and determined their absolute structures. 3. The effects of each enantiomer on cell viability and on cortisol and dehydroepiandrosterone (DHEA) secretion in the human adrenocortical cell line H295R were assessed. We also assayed the o, p'-DDD racemate and the m,p'- and p,p'-isomers. 4. The results show small but statistically significant differences in activity of the o, p'-DDD enantiomers for all parameters tested. The three DDD isomers were equally potent in decreasing cell viability, but p, p'- DDD affected hormone secretion slightly less than the o,p'- and m,p'-isomers. 5. The small chiral differences in direct effects on target cells alone do not warrant single enantiomer administration, but might reach importance in conjunction with possible stereochemical effects on pharmacokinetic processes in vivo.
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| 2. |
- Bahrami, Fariba, et al.
(författare)
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Persistent Olfactory Mucosal Metaplasia and Increased Olfactory Bulb Glial Fibrillary Acidic Protein Levels Following a Single Dose of Methylsulfonyl-dichlorobenzene in Mice: Comparison of the 2,5- and 2,6-Dichlorinated Isomers
- 2000
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 162:1, s. 49-59
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Tidskriftsartikel (refereegranskat)abstract
- Histopathology was used to characterize long-term toxic effects in the olfactory system following a single ip dose (4–65 mg/kg) of methylsulfonyl-2,6-dichlorobenzene, (2,6-(diCl-MeSO2-B)), in female NMRI mice. The effects of 2,6-(diCl-MeSO2-B) and its 2,5-chlorinated isomer, (2,5-(diCl-MeSO2-B)), on the levels of glial fibrillary acidic protein (GFAP; a biomarker for neurotoxicity) in different brain regions were examined by an enzyme-linked immunosorbent assay (ELISA). The histopathologic effects of 2,6-(diCl-MeSO2-B) were dose-, time-, and tissue-dependent. At the highest doses (16–65 mg/kg), the initial effect of 2,6-(diCl-MeSO2-B) was necrosis of the Bowman's glands, followed by a sequence of secondary events including degeneration of the olfactory neuroepithelium, repopulation of the basement membrane by a ciliated respiratorylike epithelium, fibrosis and ossification in the lamina propria, formation of bilateral polyps, angiogenesis, and disappearance of nerve bundles. Remodeling was most pronounced in the dorsal meatus of the olfactory mucosa and persisted for the duration of the experiment (46 weeks). A dose-dependent induction of GFAP in the olfactory bulb of mice treated with 2,6-(diCl-MeSO2-B) was observed at all doses examined (16–65 mg/kg). GFAP levels were highest 2 weeks after treatment (eightfold induction at 65 mg/kg) and then gradually decreased to normal within 26 weeks. The 2,5-substituted isomer (65 mg/kg) did not induce GFAP in the olfactory bulb and or toxicity in the olfactory mucosa. In conclusion, a single dose of 2,6-(diCl-MeSO2-B) results in persistent metaplasia and remodeling of the olfactory mucosa, and a long-lasting but transient induction of GFAP in the olfactory bulb. It is proposed that methylsulfonyl-2,6-dichlorobenzene may serve as an experimental tool with a unique ability to produce persistent primary and/or secondary lesions in the olfactory system of mice.
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| 3. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 4. |
- Bergman, Ingvar, et al.
(författare)
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Health-adjusted neuropsychological test norms based on 463 older Swedish car drivers
- 2016
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 57:2, s. 93-107
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for improved normative information in particular for older persons. The present study provides neuropsychological test norms on seven cognitive tests used in a sample representing the general older driving population, when uncontrolled and controlled for physical health. A group of 463 healthy Swedish car drivers, aged 65 to 84 years, participated in a medical and neuropsychological examination. The latter included tests of visual scanning, mental shifting, visual spatial function, memory, reaction time, selective attention, and simultaneous capacity. Hierarchical regression analyses demonstrated that, when uncontrolled for health, old age was associated with significant impairment on all seven tests. Education was associated with a significant advantage for all tests except most reaction time subtests. Women outperformed men on selective attention. Controlling for health did not consistently change the associations with education, but generally weakened those with age, indicating rises in normative scores of up to 0.36 SD (residual). In terms of variance explained, impaired health predicted on average 2.5%, age 2.9%, education 2.1% and gender 0.1%. It was concluded (1)that individual regression-based predictions of expected values have the advantage of allowing control for the impact of health on normative scores in addition to the adjustment for various demographic and performance-related variables and (2) that health-adjusted norms have the potential to classify functional status more accurately, to the extent that these norms diverge from norms uncontrolled for physical health.
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| 5. |
- Bergman, Ingvar, et al.
(författare)
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Neuropsychological test norms controlled for physical health : Does it matter?
- 2015
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 56:2, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to investigate the effects of physical health on neuropsychological test norms. Medical and neuropsychological data from 118 healthy volunteer controls, aged 26-91years, were collected during five recruitment occasions. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological test battery. Test-specific statistical regression-weights for age, education and gender were calculated to establish preliminary test norms. Hierarchical regression analyses demonstrated that control in addition for physical health moved best performance from age 60 to 65 for abstraction; replaced a plateau above age 70 for verbal fluency, with a continued rise in performance; eliminated significant negative influences of age on auditory learning, spatial reasoning and complex copying; reduced them on wordlist recall, psychomotor speed, visual scanning and mental shifting; and slightly reduced negative influences of low education on most verbal tests, several memory tests, and psychomotor speed, indicating rises in normative scores of up to 0.8 SD at age 80 and 0.4 SD at age 60. No differences were found at age 40. Although the sample size is not adequate to be used for normative data, the findings indicate that norms uncontrolled for health overestimate the negative influence of advanced age and low education, implying a risk of drawing false diagnostic conclusions.
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| 6. |
- Bergman, Ingvar, et al.
(författare)
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Test-retest reliability, practice effects and estimates of change: A study on the Mindmore digital cognitive assessment tool
- 2024
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Ingår i: Scandinavian Journal of Psychology. - : WILEY. - 0036-5564 .- 1467-9450.
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to establish test-retest reliability and investigate practice effects of the Mindmore cognitive assessment tool, a digital adaptation of traditional pencil and paper tests designed for self-administration. Additionally, normative change scores for the most frequently used tests were derived. A total of 149 healthy Swedish adults (aged 20-79) completed the test battery twice, 1 month apart. The battery assessed attention and processing speed, memory, language, visuospatial functions, and executive functions. Test-retest reliability, measured by ICC and Spearman coefficients, and practice effects were estimated for 22 main-scores and 33 sub-scores. Regression models were used to assess change in performance while controlling for demographics, computer equipment, testing location (online or in-laboratory) and baseline performance for 12 main-scores and nine sub-scores. Test-retest reliability was good for 11 main-scores (>= 0.70), satisfactory for five (0.60-0.69), and minimal for six (<0.60) albeit three having satisfactory sub-scores. Practice effects were observed for tests with a major speed component, but not for reaction time, sustained attention, verbal memory and naming (alternate forms), nor visuospatial functions. Trackpad negatively influenced change for one test. Demographics and testing location did not significantly affect the change scores. Our study provides support for test-retest reliability and practice effects of the Mindmore cognitive assessment tool which were comparable to those of traditional tests. These findings, together with the normative change scores, can aid researchers and clinicians in interpreting test results and distinguishing between normal variations in performance and changes indicative of clinical impairment.
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| 7. |
- Bergman, Ingvar, et al.
(författare)
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The effect of age on fluid intelligence is fully mediated by physical health
- 2013
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 57:1, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the extent to which the effect of age on cognitive ability is predicted by individual differences in physical health. The sample consisted of 118 volunteer subjects who were healthy and ranging in age from 26 to 91. The examinations included a clinical investigation, magnetic resonance imaging (MRI) brain neuroimaging, and a comprehensive neuropsychological assessment. The effect of age on fluid IQ with and without visual spatial praxis and on crystallized IQ was tested whether being fully-, partially-or non-mediated by physical health. Structural equation analyses showed that the best and most parsimonious fit to the data was provided by models that were fully mediated for fluid IQ without praxis, non-mediated for crystallized IQ and partially mediated for fluid IQ with praxis. The diseases of the circulatory and nervous systems were the major mediators. It was concluded from the pattern of findings that the effect of age on fluid intelligence is fully mediated by physical health, while crystallized intelligence is non-mediated and visual spatial praxis is partially mediated, influenced mainly by direct effects of age. Our findings imply that improving health by acting against the common age-related circulatory-and nervous system diseases and risk factors will oppose the decline in fluid intelligence with age.
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| 8. |
- Bergman, Ingvar, et al.
(författare)
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The importance of impaired physical health and age in normal cognitive aging
- 2007
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 48:2, s. 115-125
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the importance of impaired physical health and age in normal cognitive aging. In our cross-sectional, clinical and explorative study, medical and neuropsychological data from 118 voluntary healthy controls aged 26-91 years were collected from five recruitment occasions. Health was assessed according to a criterion reflecting clinical and subclinical severity. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological assessment. Regression analyses showed a significant incidence of clinical and subclinical medical disorders that explained 10.8% of the variation in cognitive performance, while age-related impairment explained 5.6%. Findings of the central nervous system were important but various other medical findings explained about half of the health-related variation. Cognitively demanding tasks were more susceptible to impaired physical health while tasks comprising salient motor- and visual spatial elements were more prone to be impaired by age. Our findings suggest (1) that impaired physical health is more important than chronological age in accounting for cognitive impairment across the adult lifespan, (2) that age and health dissociate with regard to cognitive functions affected, and (3) that selection for so-called ""super healthy"" elderly people might be justified in cognitive research. Because the prevalent diseases in normal aging are potentially preventable, the present findings promise good prospect for prevention of future cognitive disability among elderly people.
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| 9. |
- Bergman, Peter N., et al.
(författare)
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Do job demands and job control affect problem-solving?
- 2012
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Ingår i: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 42:2, s. 195-203:42, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Job Demand Control model presents combinations of working conditions that may facilitate learning, the active learning hypothesis, or have detrimental effects on health, the strain hypothesis. To test the active learning hypothesis, this study analysed the effects of job demands and job control on general problem-solving strategies. Participants: A population-based sample of 4,636 individuals (55% women, 45% men) with the same job characteristics measured at two times with a three year time lag was used. Methods: Main effects of demands, skill discretion, task authority and control, and the combined effects of demands and control were analysed in logistic regressions, on four outcomes representing general problem-solving strategies. Results: Those reporting high on skill discretion, task authority and control, as well as those reporting high demand/high control and low demand/high control job characteristics were more likely to state using problem solving strategies. Conclusions: Results suggest that working conditions including high levels of control may affect how individuals cope with problems and that workplace characteristics may affect behaviour in the non-work domain.
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| 10. |
- Bergman, Peter, et al.
(författare)
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Non-participation in the second wave of the PART study on mental disorder and its effects on risk estimates
- 2010
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Ingår i: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854. ; 56:2, s. 119-132
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Tidskriftsartikel (refereegranskat)abstract
- Background: In epidemiological studies, analyses are needed to investigate the consequences of non-response. Aims: To analyse the consequences of attrition in the second wave of the population-based PART study, which was performed three years after the first wave. Methods: Potential determinants for non-participation obtained from population registers and the first wave were analyzed. The relationships between potential determinants and reduced well-being or depressive mood in the first wave questionnaire were investigated separately for participants and non-participants in the second wave. Samples of respondents to the second wave questionnaire with reduced or not reduced well-being were summoned for interview regarding determinants of distress and disorder. The occurrence of potential determinants was compared between participants and non-participants in both groups Results: Low income, low education, non-Nordic origin, not being married and previous psychiatric diagnosis were associated with lower participation rates. These variables were similarly related to depressive mood and low psychological well-being in the first wave among participants and non-participants in the second wave. Potential determinants were not or only weakly related to participation in the interview groups. Conclusion: Although the true prevalence of distress and disorder is underestimated, the true associations between potential determinants and the outcomes seem reasonably well reproduced.
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