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| 5. |
- Kreisel, S. H., et al.
(författare)
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Deterioration of Gait and Balance over Time: The Effects of Age-Related White Matter Change - The LADIS Study
- 2013
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 35:6, s. 544-553
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care. Methods: 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i. e. ARWMC) and outcome. Results: Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology. Conclusion: Only moderate and severe ARWMC is independently associated -on average -with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.
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| 6. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Age and diagnostic performance of Alzheimer disease CSF biomarkers.
- 2012
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Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
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Tidskriftsartikel (refereegranskat)abstract
- Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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| 7. |
- Poggesi, A., et al.
(författare)
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Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study
- 2013
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 260:4, s. 1014-1021
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 +/- A 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.
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| 8. |
- Poggesi, A., et al.
(författare)
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Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And DISability) study
- 2014
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 261:6, s. 1160-1169
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 +/- A 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with a parts per thousand yen1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.
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| 13. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 14. |
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| 15. |
- Donadio, V., et al.
(författare)
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Muscle sympathetic response to arousal predicts neurovascular reactivity during mental stress
- 2012
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Ingår i: Journal of Physiology-London. - : Wiley. - 0022-3751. ; 590:12, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- Key points Mental stress (MS) is often initiated by a sensory or cognitive stimulus, which induces a brief arousal reaction followed by a longer stress phase. Both phases induce blood pressure (BP) increases whereas effects on muscle sympathetic nerve activity (MSNA) vary: in approximately 50% of healthy subjects (responders) arousal induces a brief MSNA reduction, which is absent in the remaining 50% (non-responders). We now report a link between the arousal response and neurovascular effects of MS in healthy males. Our data show that during MS, responders to arousal exhibited a significant decrease of MSNA and a lesser BP increase compared to non-responders. The whole material displayed a positive correlation between MSNA responses induced by arousal and MS. In addition, arousal induced MSNA changes correlated positively with BP changes during MS. We conclude that the MSNA response to arousal predicts MSNA and BP responses to MS.
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| 16. |
- Dutoit, Andrea P, et al.
(författare)
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Cardiac baroreflex sensitivity is not correlated to sympathetic baroreflex sensitivity within healthy, young humans.
- 2010
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Ingår i: Hypertension. - 1524-4563. ; 56:6, s. 1118-1123
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the relationship between the cardiac and sympathetic baroreflex sensitivities within healthy, young humans. The sensitivities of the cardiac and sympathetic baroreflexes were compared in 53 normotensive individuals (28 men and 25 women; age: 24.0 ± 0.9 years; body mass index: 24.0 ± 0.3 cm/kg², mean ± SEM). Heart rate, arterial blood pressure, and peroneal muscle sympathetic nerve activity were recorded under resting conditions (heart rate: 58 ± 1 bpm; systolic blood pressure: 126 ± 2 mm Hg; diastolic blood pressure: 72 ± 1 mm Hg; mean arterial blood pressure: 89 ± 1 mm Hg; muscle sympathetic nerve activity: 18 ± 1 bursts per min) and during rapid changes in blood pressure induced by sequential boluses of nitroprusside and phenylephrine. Cardiac and sympathetic baroreflex sensitivities were analyzed using the slopes of the linear portions of the muscle sympathetic nerve activity-diastolic blood pressure and R-R interval-systolic blood pressure relationships, respectively. When individual cardiac baroreflex sensitivity was compared with sympathetic baroreflex sensitivity, no correlation (R-R interval: r = -0.13; heart rate: r = 0.21) was observed when studied as a group. Analysis by sex unveiled a correlation in women between the cardiac and sympathetic baroreflex sensitivities (R-R interval: r = -0.54; P = 0.01; no correlation with hazard ratio: r = 0.29). No relationship was found in men (R-R interval: r = 0.17; heart rate: r = 0.12). These results indicate that, although both cardiac and sympathetic efferents function in baroreflex control of arterial pressure, there is no correlation in their sensitivities within healthy normotensive humans. However, sex-stratified data indicate that sex-based differential correlations might exist.
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| 17. |
- Eriksson, Leif, et al.
(författare)
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Newborn care and knowledge translation - perceptions among primary health care staff in northern Vietnam
- 2011
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 6, s. 29-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nearly four million neonatal deaths occur annually in the world despite existing evidence-based knowledge with the potential to prevent many of these deaths. Effective knowledge translation (KT) could help to bridge this know-do gap in global health. The aim of this study was to explore aspects of KT at the primary healthcare level in a northern province in Vietnam. METHODS: Six focus-group discussions were conducted with primary healthcare staff members who provided neonatal care in districts that represented three types of geographical areas existing in the province (urban, rural, and mountainous). Recordings were transcribed verbatim, translated into English, and analyzed using content analysis. RESULTS: We identified three main categories of importance for KT. Healthcare staff used several channels for acquisition and management of knowledge (1), but none appeared to work well. Participants preferred formal training to reading guideline documents, and they expressed interest in interacting with colleagues at higher levels, which rarely happened. In some geographical areas, traditional medicine (2) seemed to compete with evidence-based practices, whereas in other areas it was a complement. Lack of resources, low frequency of deliveries and, poorly paid staff were observed barriers to keeping skills at an adequate level in the healthcare context (3). CONCLUSIONS: This study indicates that primary healthcare staff work in a context that to some extent enables them to translate knowledge into practice. However, the established and structured healthcare system in Vietnam does constitute a base where such processes could be expected to work more effectively. To accelerate the development, thorough considerations over the current situation and carefully targeted actions are required.
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| 18. |
- Firbank, M. J., et al.
(författare)
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Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study
- 2012
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:1, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Background Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear. Aims To investigate the relationship between baseline and incident depression and progression of white matter changes. Method In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale. Results Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline. Conclusions Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.
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| 20. |
- Fuks, Jonas M, et al.
(författare)
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GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii
- 2012
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:12, s. e1003051-
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Tidskriftsartikel (refereegranskat)abstract
- During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondii for spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABA(A) receptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABA(A) receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DC in vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
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| 21. |
- Gharahi Ghehi, N., et al.
(författare)
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N2O and NO emission from the Nyungwe tropical highland rainforest in Rwanda
- 2014
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Ingår i: Geoderma Regional. - 2352-0094. ; 2-3, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forest soils are a significant source for N2O and NO. Current estimates of N2O and NO emissions are uncertain due to the limited number of fieldmeasurements and model input data. Furthermore, considerable spatial and temporal variability exists due to variation of soil properties, vegetation characteristics and meteorology.We used a process-based model (ForestDNDC-tropica) to estimate N2O and NO emissions from the entire (970 km2) tropical highland forest (Nyungwe) in southwestern Rwanda. Scaling these results to that regional level using legacy soil, meteorological and simulated vegetation data we found in most cases agreement between N2O and NO measurements and model predictions. Limited agreement was found for acid soils with high clay content and reduced metals, indicating that abiotic N2O and NO forming processes in acidic soils might be under-represented in the current ForestDNDC-tropica model. The Nyungwe forest was estimated to emit 439 t N2O-N year−1 (2.8– 5.5 kg N2O-N ha−1 year−1) and 244 t NO-N year−1 (0.8–5.1 kg N ha−1 year−1), corroborating previous studies in tropical forests and highlighting that also tropical highland rainforest soils are a major source of atmospheric N2O and NO. The uncertainty for the N2O and NO emission estimates was 153 and 50 t N2O-N year−1 and 36 and 16 t NO-N year−1 considering uncertainty in model input data and annual variability, respectively. The results showed that soil bulk density and pH were the most influential factors driving spatial variation and model uncertainty. To improve global model-based estimates of N2O and NO emission from tropical forest focus should therefore also be oriented in delivering more detailed soil and vegetation data.
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| 22. |
- Glover, A. G., et al.
(författare)
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A live video observatory reveals temporal processes at a shelf-depth whale-fall
- 2010
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Ingår i: Cahiers De Biologie Marine. - 0007-9723. ; 51:4, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- There have been very few studies of temporal processes at chemosynthetic ecosystems, even at relatively more accessible shallow water sites. Here we report the development and deployment of a simple cabled video observatory at 30 m water depth in Gullmarsfjorden, Sweden. The camera provides a live video feed to the internet of faunal activity in the experiments, which to date have included 5 separate whale-fall deployments. Our data suggest that the time to decomposition of small cetacean carcasses at shelf-depth settings is considerably slower than at deep-sea sites. We have also provided a new methodology for the deployment of low-cost live video observatories at up to 30 m water depth, which can be used both for research and outreach activities.
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| 23. |
- Hertzen, Erika, et al.
(författare)
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M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages
- 2010
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:6, s. 534-545
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-kappa B signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury. Copyright (C) 2010 S. Karger AG, Basel
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| 24. |
- Jokinen, H., et al.
(författare)
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Diffusion changes predict cognitive and functional outcome: The LADIS study
- 2013
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 73:5, s. 576-583
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Tidskriftsartikel (refereegranskat)abstract
- Objective A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings. Methods A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities. Results The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes. Interpretation DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality. Ann Neurol 2013;73:576–583
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| 25. |
- Jokinen, H, et al.
(författare)
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Incident lacunes influence cognitive decline: the LADIS study.
- 2011
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 76:22, s. 1872-8
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Tidskriftsartikel (refereegranskat)abstract
- In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
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| 26. |
- Lidell, Martin, 1970, et al.
(författare)
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The Adipocyte-Expressed Forkhead Transcription Factor Foxc2 Regulates Metabolism Through Altered Mitochondrial Function
- 2011
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Ingår i: Diabetes. - 0012-1797. ; 60:2, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous findings demonstrate that enhanced expression of the forkhead transcription factor Foxc2 in adipose tissue leads to a lean and insulin-sensitive phenotype. These findings prompted us to further investigate the role of Foxc2 in the regulation of genes of fundamental importance for metabolism and mitochondrial function. RESEARCH DESIGN AND METHODS: The effects of Foxc2 on expression of genes involved in mitochondriogenesis and mitochondrial function were assessed by quantitative real-time PCR. The potential of a direct transcriptional regulation of regulated genes was tested in promoter assays, and mitochondrial morphology was investigated by electron microscopy. Mitochondrial function was tested by measuring oxygen consumption and extracellular acidification rates as well as palmitate oxidation. RESULTS: Enhanced expression of FOXC2 in adipocytes or in cells with no endogenous Foxc2 expression induces mitochondriogenesis and an elongated mitochondrial morphology. Together with increased aerobic metabolic capacity, increased palmitate oxidation, and upregulation of genes encoding respiratory complexes and of brown fat-related genes, Foxc2 also specifically induces mitochondrial fusion genes in adipocytes. Among tested forkhead genes, Foxc2 is unique in its ability to trans-activate the nuclear-encoded mitochondrial transcription factor A (mtTFA/Tfam) gene--a master regulator of mitochondrial biogenesis. In human adipose tissue the expression levels of mtTFA/Tfam and of fusion genes also correlate with that of Foxc2. CONCLUSIONS: We previously showed that a high-calorie diet and insulin induce Foxc2 in adipocytes; the current findings identify a previously unknown role for Foxc2 as an important metabo-regulator of mitochondrial morphology and metabolism.
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| 28. |
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| 29. |
- Nga, Nguyen T., et al.
(författare)
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Perinatal services and outcomes in Quang Ninh province, Vietnam
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:10, s. 1478-1483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We report baseline results of a community-based randomized trial for improved neonatal survival in Quang Ninh province, Vietnam (NeoKIP; ISRCTN44599712). The NeoKIP trial seeks to evaluate a method of knowledge implementation called facilitation through group meetings at local health centres with health staff and community key persons. Facilitation is a participatory enabling approach that, if successful, is well suited for scaling up within health systems. The aim of this baseline report is to describe perinatal services provided and neonatal outcomes. Methods: Survey of all health facility registers of service utilization, maternal deaths, stillbirths and neonatal deaths during 2005 in the province. Systematic group interviews of village health workers from all communes. A Geographic Information System database was also established. Results: Three quarters of pregnant women had >= 3 visits to antenatal care. Two hundred and five health facilities, including 18 hospitals, provided delivery care, ranging from 1 to 3258 deliveries/year. Totally there were 17 519 births and 284 neonatal deaths in the province. Neonatal mortality rate was 16/1000 live births, ranging from 10 to 44/1000 in the different districts, with highest rates in the mountainous parts of the province. Only 8% had home deliveries without skilled attendance, but those deliveries resulted in one-fifth of the neonatal deaths. Conclusion: A relatively good coverage of perinatal care was found in a Vietnamese province, but neonatal mortality varied markedly with geography and level of care. A remaining small proportion of home deliveries generated a substantial part of mortality.
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| 33. |
- Saeed, A., et al.
(författare)
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7 alpha-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the integrity of the blood-brain barrier
- 2014
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 55:2, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7 alpha-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cerebrospinal fluid (CSF) at a relatively high concentration. A simple and accurate method was developed for assay of 7-HOCA in CSF based on isotope dilution-mass spectrometry and use of H-2(4)-labeled internal standard. The concentration of this metabolite was found to be markedly increased in CSF from patients with a dysfunctional BBB. There was a high correlation between the levels of 7-HOCA in CSF and the CSF/serum albumin ratio. The concentration of 7-HOCA in CSF was not significantly affected by neurodegeneration. Our findings suggest that 7-HOCA could be used as a diagnostic marker for conditions with a dysfunctional BBB.
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| 34. |
- Sagare, Abhay P, et al.
(författare)
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Impaired Lipoprotein Receptor-Mediated Peripheral Binding of Plasma Amyloid-β is an Early Biomarker for Mild Cognitive Impairment Preceding Alzheimer's Disease.
- 2011
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 24:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Soluble circulating low density lipoprotein receptor-related protein-1 (sLRP) provides key plasma binding activity for Alzheimer's disease (AD) amyloid-β peptide (Aβ). sLRP normally binds 70-90% of plasma Aβ preventing free Aβ access to the brain. In AD, Aβ binding to sLRP is compromised by increased levels of oxidized sLRP which does not bind Aβ. Here, we determined plasma oxidized sLRP and Aβ40/42 sLRP-bound, other proteins-bound and free plasma fractions, cerebrospinal fluid (CSF) tau/Aβ42 ratios, and mini-mental state examination (MMSE) scores in patients with mild cognitive impairment (MCI) who progressed to AD (MCI-AD, n = 14), AD (n = 14) and neurologically healthy controls (n = 14) recruited from the Göteborg MCI study. In MCI-AD patients prior to conversion to AD and AD patients, the respective increases in oxidized sLRP and free plasma Aβ40 and Aβ42 levels were 4.9 and 3.7-fold, 1.8, and 1.7-fold and 4.3 and 3.3-fold (p < 0.05, ANOVA with Tuckey post-hoc test). In MCI-AD and AD patients increases in oxidized sLRP and free plasma Aβ40 and Aβ42 correlated with increases in CSF tau/Aβ42 ratios and reductions in MMSE scores (p < 0.05, Pearson analysis). A heterogeneous group of 'stable' MCI patients that was followed over 2-4 years (n = 24) had normal CSF tau/Aβ42 ratios but increased oxidized sLRP levels (p < 0.05, Student's t test). Data suggests that a deficient sLRP-Aβ binding might precede and correlate later in disease with an increase in the tau/Aβ42 CSF ratio and global cognitive decline in MCI individuals converting into AD, and therefore is an early biomarker for AD-type dementia.
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| 35. |
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| 36. |
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| 37. |
- Schmidt, R., et al.
(författare)
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White Matter Lesion Progression in LADIS Frequency, Clinical Effects, and Sample Size Calculations
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:10, s. 2643-2647
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. Methods-Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. Results-WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. Conclusions-WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure. (Stroke. 2012; 43:2643-2647.)
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| 38. |
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| 39. |
- Skoglund, Lena, et al.
(författare)
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Novel Progranulin Mutation Detected in 2 Patients With FTLD
- 2011
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Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 25:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
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| 40. |
- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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| 41. |
- Verdelho, A., et al.
(författare)
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Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study
- 2013
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 84:11, s. 1250-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objective Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). Methods The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. Results 639 subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. Conclusions DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction
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| 42. |
- Verdelho, A., et al.
(författare)
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Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia Results From the LADIS (Leukoaraiosis and Disability) Study
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:12, s. 3331-3335
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. Methods-The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. Results-Six hundred thirty-nine subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: beta=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (beta=-0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia (beta=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes. Conclusions-Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently. (Stroke. 2012; 43: 3331-3335.)
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| 43. |
- Wallin, Lars, et al.
(författare)
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Implementing knowledge into practice for improved neonatal survival : a cluster-randomised, community-based trial in Quang Ninh province, Vietnam
- 2011
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Ingår i: BMC health services research. - : Springer Science and Business Media LLC. - 1472-6963. ; 11, s. 239-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Globally, almost 4 million newborns die during the first 4 weeks of life every year. By increased use of evidence-based knowledge in the healthcare system a large proportion of these neonatal deaths could be prevented. But there is a severe lack of knowledge on effective methods for successful implementation of evidence into practice, particularly in low- and middle-income countries. Recent studies have demonstrated promising results with increased survival among both mothers and newborns using community-based approaches. In Vietnam evidence-based guidelines on reproductive health were launched in 2003 and revised in 2009. The overall objective of the current project is to evaluate if a facilitation intervention on the community level, with a problem-solving approach involving local representatives if the healthcare system and the community, results in improvements of neonatal health and survival.METHODS/DESIGN: The study, which has been given the acronym NeoKIP (Neonatal Health - Knowledge Into Practice), took place in 8 districts composed by 90 communes in a province in northern Vietnam, where neonatal mortality rate was 24/1000 in 2005. A cluster randomised design was used, allocating clusters, as defined as a commune and its correponding Commune Health Center (CHC) to either intervention or control arm. The facilitation intervention targeted staff at healthcare centres and key persons in the communes. The facilitator role was performed by lay women (Women's Union representatives) using quality improvement techniques to initiate and sustain improvement processes targeting identified problem areas. The intervention has been running over 3 years and data were collected on the facilitation process, healthcare staff knowledge in neonatal care and their behaviour in clinical practice, and reproductive and perinatal health indicators. Primary outcome is neonatal mortality.DISCUSSION: The intervention is participatory and dynamic, focused on developing a learning process and a problem-solving cycle. The study recognises the vital role of the local community as actors in improving their own and their newborns' health, and applies a bottom-up approach where change will be accomplished by an increasing awareness at and demand from grass root level. By utilising the existing healthcare structure this intervention may, if proven successful, be well suited for scaling up.TRIAL REGISTRATION: Current Controlled Trials ISRCTN44599712.
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| 44. |
- Wallin, M. Carlsson, et al.
(författare)
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Apgar score and perinatal death after one previous caesarean delivery
- 2010
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Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 117:9, s. 1088-1097
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the impact of the indication for a previous caesarean section on the outcome of a subsequent delivery. Design Population-based cohort study. Setting Sweden. Population Women with two deliveries between 1987 and 2007 identified using the Swedish Medical Birth Registry. Methods The outcome of 69 133 pregnancies after one caesarean section was compared with the outcome of 487 610 pregnancies following one vaginal delivery. The indication for the first caesarean section was estimated using a new hierarcharchical system based on information from birth records. Main outcome measures Perinatal death, low Apgar score (less than seven at 5 minutes). Results Infants of women with one previous caesarean section were at increased risk of low Apgar score compared with infants of women with one previous vaginal delivery (OR, 2.0; 95% CI, 1.9-2.1). The risk estimate was reduced when adjustment for maternal and fetal/infant characteristics was made (OR, 1.6; 95% CI, 1.5-1.8). The corresponding crude and adjusted odds ratios for perinatal death were 1.6 (95% CI, 1.4-1.7) and 1.1 (95% CI, 1.0-1.2), respectively. The infant outcome of the delivery after one caesarean section was mainly dependent on the indication for the first-delivery caesarean section and, when no medical indication was present, no increase in risk was detected. Conclusions Infants of women with one previous caesarean section were at increased risk of low Apgar score and/or perinatal death compared with infants of women with one previous vaginal delivery. The results suggest that medical conditions, not the previous caesarean section per se, contributed to the increase in risk.
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| 45. |
- Wallin, S., et al.
(författare)
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Biomonitoring study of deoxynivalenol exposure and association with typical cereal consumption in Swedish adults
- 2013
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Ingår i: World Mycotoxin Journal. - 1875-0710 .- 1875-0796. ; 6:4, s. 439-448
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Tidskriftsartikel (refereegranskat)abstract
- Deoxynivalenol (DON) is a mycotoxin of the trichothecene family commonly found in cereals infested with different Fusarium species. DON acts primarily on the gastrointestinal and immune system and is suspected to be an underlying agent causing several outbreaks of gastrointestinal disorder among humans, which prompts studies of human exposure and estimations of intake among populations. However, assessing human exposure to mycotoxins is associated with several difficulties. Therefore, a study was undertaken among adults (18-80 years) in a subgroup of Riksmaten, the Swedish national survey investigating dietary habits, examining both the association between urinary DON concentration and dietary intake of cereals, and estimations of daily DON intake. The results indicate that exposure to DON is common among Swedish adults, as this mycotoxin was detected in 292 out of 326 urine samples (90%) at levels ranging from non-detectable to 65.8 ng DON/mI urine with a median level of 2.9 ng/ml. Furthermore, urinary DON (ng/mg creatinine) was associated with intake (g/day) of total cereal grain as well as whole grain. Urinary DON was also significantly associated with breakfast cereals and porridge consumption (P<0.05). Estimated DON intake in this study ranged between 2.5 and 5,443 ng/kg body weight (bw). 1% of the individuals had estimated intakes above the group provisional maximum tolerable daily intake (PMTDI; 1 mu g/kg), whereas the mean and median intakes of 159 and 84 ng DON/kg bw, respectively, were considerably below the PMTDI. Along with the toxicological profile of DON, no serious health implications are to be expected for the majority of Swedish adults, although a potential health concern remains for some high cereal consumers. In conclusion, biomonitoring could prove to be a valuable tool for observing DON exposure among populations.
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| 46. |
- Weidner, Jessica M., et al.
(författare)
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Rapid cytoskeleton remodelling in dendritic cells following invasion by Toxoplasma gondii coincides with the onset of a hypermigratory phenotype
- 2013
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 15:10, s. 1735-1752
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Tidskriftsartikel (refereegranskat)abstract
- Host cell manipulation is an important feature of the obligate intracellular parasite Toxoplasma gondii. Recent reports have shown that the tachyzoite stages subvert dendritic cells (DC) as a conduit for dissemination (Trojan horse) during acute infection. To examine the cellular basis of these processes, we performed a detailed analysis of the early events following tachyzoite invasion of human monocyte-derived DC. We demonstrate that within minutes after tachyzoite penetration, profound morphological changes take place in DC that coincide with a migratory activation. Active parasite invasion of DC led to cytoskeletal actin redistribution with loss of adhesive podosome structures and redistribution of integrins (CD18 and CD11c), that concurred with the onset of DC hypermotility in vitro. Inhibition of parasite rhoptry secretion and invasion, but not inhibition of parasite or host cell protein synthesis, abrogated the onset of morphological changes and hypermotility in DC dose-dependently. Also, infected DC, but not by-stander DC, exhibited upregulation of C-C chemokine receptor 7 (CCR7). Yet, the onset of parasite-induced DC hypermotility preceded chemotactic migratory responsesin vitro. Collectively, present data reveal that invasion of DC by T. gondii initiates a series of regulated events, including rapid cytoskeleton rearrangements, hypermotility and chemotaxis, that promote the migratory activation of DC.
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| 47. |
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