| 1. |
- Chibnik, L. B., et al.
(författare)
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Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium
- 2017
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 32:10, s. 931-938
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.
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| 2. |
- Labeau, S., et al.
(författare)
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Evidence-based guidelines for the prevention of ventilator-associated pneumonia : results of a knowledge test among European intensive care nurses
- 2008
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 70:2, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- As part of a needs analysis preceding the development of an e-learning platform on infection prevention, European intensive care unit (ICU) nurses were subjected to a knowledge test on evidence-based guidelines for preventing ventilator-associated pneumonia (VAP). A validated multiple-choice questionnaire was distributed to 22 European countries between October 2006 and March 2007. Demographics included nationality, gender, ICU experience, number of ICU beds and acquisition of a specialised degree in intensive care. We collected 3329 questionnaires (response rate 69.1%). The average score was 45.1%. Fifty-five percent of respondents knew that the oral route is recommended for intubation; 35% knew that ventilator circuits should be changed for each new patient; 38% knew that heat and moisture exchangers were the recommended humidifier type, but only 21% knew that these should be changed once weekly; closed suctioning systems were recommended by 46%, and 18% knew that these must be changed for each new patient only; 51% and 57%, respectively, recognised that subglottic drainage and kinetic beds reduce VAP incidence. Most (85%) knew that semi-recumbent positioning prevents VAP. Professional seniority and number of ICU beds were shown to be independently associated with better test scores. Further research may determine whether low scores are related to a lack of knowledge, deficiencies in training, differences in what is regarded as good practice, and/or a lack of consistent policy.
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| 3. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 4. |
- Eék, Niels, 1980, et al.
(författare)
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Efficacy of an Internet-Based Community Reinforcement and Family Training Program to Increase Treatment Engagement for AUD and to Improve Psychiatric Health for CSOs: A Randomized Controlled Trial
- 2020
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Ingår i: Alcohol and alcoholism (Oxford, Oxfordshire). - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 55:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Community Reinforcement Approach and Family Training (CRAFT) is a support program for concerned significant others (CSOs) to identified persons (IPs) with alcohol use disorders, with the purpose of engaging IPs to treatment and to improve CSO functioning. The purpose of the present study was to investigate the efficacy of an internet-based version of CRAFT (iCRAFT). METHODS: Randomized controlled trial comparing iCRAFT with a wait-list (WL) condition with a nation-wide uptake in Sweden. A total of 94 CSOs to a treatment refusing IP, who described the IP according to DSM-IV criteria for alcohol dependence or abuse, were included in the study. iCRAFT consisted of five weekly administered therapist-guided modules with the following content: (a) improve CSOs' own mental health, (b) improve the CSOs skills in asking the IP to seek treatment, (c) positive communication skills training, (d) contingency management of IP drinking behavior. Main outcome measure was IPs initiative to seek treatment measured at 24weeks. Secondary outcomes were IP's daily alcohol consumption, CSOs mental health, quality of life and relational satisfaction. RESULTS: Of 94 participants, 15 CSOs reported IP treatment initiative during the study period. Of these, 10 belonged to the iCRAFT condition and five to the WL condition. The difference between conditions was nonsignificant, and the results were inconclusive. Participants in iCRAFT showed short-term improvements regarding depressive symptoms, quality of life and relational happiness. CONCLUSION: This study was unable to demonstrate substantial changes in the iCRAFT program regarding IP treatment seeking or CSO mental health. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press.
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| 5. |
- Jonasson, Lars S., et al.
(författare)
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Dopamine release in nucleus accumbens during rewarded task switching measured by [C-11]raclopride
- 2014
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 99, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D-2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [C-11]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [C-11]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.
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| 6. |
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| 7. |
- Ahlberg, M, et al.
(författare)
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Moving forward in life after being an on-looker in intensive care partner's experience of group-communication
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background: Partners have a burdensome time during and after their partners’ intensive care period. They may appear to be coping welloutwardly but inside feel vulnerable and lost. Evaluated interventions for partners on this aspect are limited.Aim: The aim of this study was to describe the experience of participating in group communication with other partners of former intensivecare patients.Design: The study has a descriptive intervention-based design where group communication for partners of former, surviving intensive careunit (ICU) patients was evaluated.Methods: A strategic selection was made of adult partners to former adult intensive care patients (n=15), 5 men and 10 women, aged37–89 years. Two group communication sessions lasting 2 h were held at monthly intervals with three to five partners. The partners later wrote,in a notebook, about their feelings of participating in group communications. To deepen the understanding of the impact of the sessions, six ofthe partners were interviewed. Content analysis was used to analyse the notebooks and the interviews.Findings: Three categories were identified: (1) Emotional impact, the partners felt togetherness and experienced worries and gratitude, (2)Confirmation, consciousness through insight and reflection and (3) The meeting design, group constellation and recommendation to participatein group communication.Conclusion: Partners of an intensive care patient are on a journey, constantly trying to adapt to the new situation and find new strategiesto ever-changing circumstances. Group communications contributed to togetherness and confirmation. To share experiences with others is oneway for partners to be able to move forward in life.Relevance to clinical practice: Group communication with other patients’ partners eases the process of going through the burden ofbeing a partner to an intensive care patient. Group communications needs to be further developed and evaluated to obtain consensus andevidence for the best practice.Key words: Communication • Content analysis • Intensive care • Nursing • Partners
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| 8. |
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| 9. |
- Bellander, M, et al.
(författare)
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Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement
- 2011
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Ingår i: NEUROPSYCHOLOGIA. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 49:7, s. 1938-1942
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Tidskriftsartikel (refereegranskat)abstract
- LMX1A is a transcription factor involved in the development of dopamine (DA)-producing neurons in midbrain. Previous research has shown that allelic variations in three LMX1A single nucleotide polymorphisms (SNPs) were related to risk of Parkinson's disease (PD), suggesting that these SNPs may influence the number of mesencephalic DA neurons. Prompted by the established link between striatal DA functions and working memory (WM) performance, we examined two of these SNPs in relation to the ability to benefit from 4 weeks of WM training. One SNP (rs4657412) was strongly associated with the magnitude of training-related gains in verbal WM. The allele linked to larger gains has previously been suggested to be associated with higher dopaminergic nerve cell density. No differential gains of either SNP were observed for spatial WM, and the genotype groups were also indistinguishable in tests of attention, interference control, episodic memory, perceptual speed, and reasoning for both SNPs. This pattern of data is in agreement with previous findings from our group, suggesting that cognitive effects of DA-related genes may be more easily detected in a training context than for single-assessment performance scores.
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| 10. |
- Broman, T, et al.
(författare)
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Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters
- 2011
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Ingår i: International Journal of Microbiology. - : Hindawi Publishing Corporation. - 1687-918X .- 1687-9198. ; 2011, s. Article ID 851946-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.
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| 11. |
- Burzynska, A Z, et al.
(författare)
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Age-related differences in white matter microstructure : region-specific patterns of diffusivity.
- 2010
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Ingår i: NeuroImage. - San Diego ; Orlando, Fla : Elsevier BV. - 1053-8119 .- 1095-9572. ; 49:3, s. 2104-2112
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Tidskriftsartikel (refereegranskat)abstract
- We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.
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| 12. |
- Burzynska, A Z, et al.
(författare)
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Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance
- 2011
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 21:10, s. 2261-2271
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Tidskriftsartikel (refereegranskat)abstract
- We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.
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| 13. |
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| 14. |
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| 15. |
- Bäckman, Karin, et al.
(författare)
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Deep venous thrombosis : A new task for primary health care - A randomised economic study of outpatient and inpatient treatment
- 2004
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 22:1, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- Objective - A health economic evaluation of two alternative treatment settings, inpatient care and outpatient care, for acute deep venous thrombosis. Design - A randomised multicentre trial in a defined population in regular clinical practice. Setting - Hospitals and related health care centres in the Jönköping county council in Sweden. Interventions - Patients were randomised to either an inpatient strategy (n = 66) or an outpatient strategy (n = 65) using low-molecular-weight heparin, dalteparin, administered subcutaneously once daily and adjusted for body weight. Subjects - Of 224 eligible patients, 131 entered the trial and 124 completed the economic part of the study. Main outcome measures - Direct medical and direct non-medical costs during a 3-month period. Results - Total direct costs were higher for those in the inpatient strategy group, i.e. Swedish Crowns (SEK) 16 400 per patient (Euro 1899) compared to SEK 12 100 per patient (Euro 1405) in the outpatient strategy group (p < 0.001). More patients in the outpatient group received assistance when they returned home. Few patients in either group reported sick leave. There was no difference in total number of days between the two groups. Conclusions - Total direct costs were significantly lower for the outpatient treatment strategy for deep venous thrombosis compared to the inpatient treatment strategy. No significant difference in health impact could be detected. Deep venous thrombosis can to a greater extent than previously be treated in primary care, safely, at a lower cost, and in accordance with patient preferences.
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| 16. |
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| 17. |
- Bäckman, Lars, et al.
(författare)
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Effects of working-memory training on striatal dopamine release
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 333:6043, s. 718-
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Tidskriftsartikel (refereegranskat)abstract
- Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.
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| 18. |
- Chapman, Jason W, et al.
(författare)
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Adaptive strategies in nocturnally migrating insects and songbirds: contrasting responses to wind.
- 2016
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Ingår i: Journal of Animal Ecology. - : Wiley. - 1365-2656 .- 0021-8790. ; 85:1, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- 1. Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, i.e. by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. 2. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. 3. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. 4. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. 5. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within. This article is protected by copyright. All rights reserved.
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| 19. |
- Chapman, Jason W., et al.
(författare)
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Detection of flow direction in high-flying insect and songbird migrants
- 2015
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:17, s. 751-752
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Tidskriftsartikel (refereegranskat)abstract
- Goal-oriented migrants travelling through the sea or air must cope with the effect of cross-flows during their journeys if they are to reach their destination [1–3] . In order to counteract flow-induced drift from their preferred course, migrants must detect the mean flow direction, and integrate this information with output from their internal compass, to compensate for the deflection. Animals can potentially sense flow direction by two nonexclusive mechanisms: either indirectly, by visually assessing the effect of the current on their movement direction relative to the ground; or directly, via intrinsic properties of the current [4] . Here, we report the first evidence that nocturnal compass-guided insect migrants use a turbulence-mediated mechanism for directly assessing the wind direction hundreds of metres above the ground. By comparison, we find that nocturnally-migrating songbirds do not use turbulence to detect the flow; instead they rely on visual assessment of wind-induced drift to indirectly infer the flow direction.
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| 20. |
- Dintica, Christina S., et al.
(författare)
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Tooth loss is associated with accelerated cognitive decline and volumetric brain differences : a population-based study
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 67, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Tooth loss has been related to cognitive impairment; however, its relation to structural brain differences in humans is unknown. Dementia-free participants (n = 2715) of age >= 60 years were followed up for up to 9 years. A subsample (n = 394) underwent magnetic resonance imaging at baseline. Information on tooth loss was collected at baseline, and cognitive function was assessed using the Mini-Mental State Examination at baseline and at follow-ups. Data were analyzed using linear mixed effects models and linear regression models. At baseline, 404 (14.9%) participants had partial tooth loss, and 206 (7.6%) had complete tooth loss. Tooth loss was significantly associated with a steeper cognitive decline (beta: -0.18, 95% confidence interval [CI]: -0.24 to -0.11) and remained significant after adjusting for or stratifying by potential confounders. In cross-sectional analyses, persons with complete or partial tooth loss had significantly lower total brain volume (beta: -28.89, 95% CI: -49.33 to -8.45) and gray matter volume (beta: -22.60, 95% CI: -38.26 to -6.94). Thus, tooth loss may be a risk factor for accelerated cognitive aging.
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| 21. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Effect of self-managed lifestyle treatment on glycemic control in patients with type 2 diabetes
- 2022
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Ingår i: npj Digital Medicine. - : Nature Research. - 2398-6352. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973). Users of the tool had reduced blood glucose, both compared with randomized and matched controls (involving 158 and 204 users, respectively), as well as improved systolic blood pressure, body weight and insulin resistance. The improvement was sustained during the entire follow-up (average 730 days). A pathophysiological subgroup of obese insulin-resistant individuals had a pronounced glycemic response, enabling identification of those who would benefit in particular from lifestyle treatment. Natural language processing showed that the metabolic improvement was coupled with the self-reflective element of the tool. The treatment is cost-saving because of improved risk factor control for cardiovascular complications. The findings open an avenue for self-managed lifestyle treatment with long-term metabolic efficacy that is cost-saving and can reach large numbers of people. © 2022, The Author(s).
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Gustafson, Deborah, 1966, et al.
(författare)
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Leptin and dementia over 32 years-The Prospective Population Study of Women
- 2012
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 8:4, s. 272-277
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have shown that high mid-life central adiposity may increase the risk for dementia after 32 years. Leptin, an adipose tissue hormone, is correlated with adiposity measures and may contribute to a better etiological understanding of the relationship between high adiposity and dementia. We explored the relationship between serum leptin in mid-life and dementia, which is a late-life outcome. Methods: A longitudinal cohort study, the Prospective Population Study of Women, in Gothenburg, Sweden, includes a representative sample of 1462 women followed from mid-life ages of 38 to 60 years to late-life ages of 70 to 92 years. Women were examined in 1968, 1974, 1980, 1992, and 2000 using neuropsychiatric, anthropometric, clinical, and other measurements. Serum leptin was measured on samples collected at the 1968 baseline examination, after storage at -20 degrees C for 29 years. Cox proportional hazards regression models estimated incident dementia risk by baseline leptin. Logistic regression models related leptin levels to dementia among surviving participants 32 years later. All models were adjusted for multiple potential confounders. Results: Mid-life leptin was not related to dementia risk using Cox or logistic regression models. This was observed despite positive baseline correlations between leptin and adiposity measures, and given our previous report of high mid-life waist-to-hip ratio being related to a twofold higher dementia risk. Conclusions: Leptin is not a mid-life marker of late-life dementia risk in this population sample of Swedish women born between 1908 and 1930. (C) 2012 The Alzheimer's Association. All rights reserved.
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| 27. |
- Henriksson, Richard, et al.
(författare)
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PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain
- 2014
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier. - 0006-3002 .- 1878-2434. ; 1839:11, s. 1226-1232
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Tidskriftsartikel (refereegranskat)abstract
- The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.
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| 28. |
- Kalpouzos, Grégoria, et al.
(författare)
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Impact of negative emotion on the neural correlates of long-term recognition in younger and older adults
- 2012
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 6:74, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Some studies have suggested that the memory advantage for negative emotional information over neutral information (“negativity effect”) is reduced in aging. Besides the fact that most findings are based on immediate retrieval, the neural underpinnings of long-term emotional memory in aging have so far not been investigated. To address these issues, we assessed recognition of neutral and negative scenes after 1- and 3-week retention intervals in younger and older adults using functional magnetic resonance imaging. We further used an event-related design in order to disentangle successful, false, and true recognition. This study revealed four key findings: (1) increased retention interval induced an increased rate of false recognitions for negative scenes, canceling out the negativity effect (present for hit rates only) on discrimination in both younger and older adults; (2) in younger, but not older, adults, reduced activity of the medial temporal lobe was observed over time for neutral scenes, but not for negative scenes, where stable or increased activity was seen; (3) engagement of amygdala (AMG) was observed in older adults after a 3-week delay during successful recognition of negative scenes (hits vs. misses) in comparison with neutral scenes, which may indicate engagement of automatic processes, but engagement of ventrolateral prefrontal cortex was unrelated to AMG activity and performance; and (4) after 3 weeks, but not after 1 week, true recognition of negative scenes was characterized by more activity in left hippocampus and lateral occipito-temporal regions (hits vs. false alarms). As these regions are known to be related to consolidation mechanisms, the observed pattern may indicate the presence of delayed consolidation of true memories. Nonetheless, older adults’ low performance in discrimination of negative scenes could reflect the fact that overall, after long delays of retention, they rely more on general information rather than on perceptual detail in making recognition judgments.
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| 29. |
- Kivipelto, M, et al.
(författare)
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Homocysteine and holo-transcobalamin and the risk of dementia and Alzheimers disease : a prospective study.
- 2009
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Ingår i: European journal of neurology : the official journal of the European Federation of Neurological Societies. - : Wiley. - 1468-1331 .- 1351-5101. ; 16:7, s. 808-813
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated total homocysteine (tHcy) levels may be caused by vitamin B12 deficiency and are linked to Alzheimers disease (AD) in some studies, although the evidence is mixed. Another marker of vitamin B12 deficiency, holo-transcobalamin (holo-TC), has not been studied in a prospective setting. OBJECTIVE: To investigate the association between tHcy and holo-TC and the subsequent development of dementia and AD in a prospective study. METHODS: A sub-sample of 228 non-demented subjects was taken from the Kungsholmen Project, a population-based longitudinal study amongst persons 75+ years. tHcy and holo-TC were analysed at baseline. RESULTS: Increasing tHcy levels were related to an increased risk of dementia (n = 83) and AD (n = 61) after a mean follow-up time of 6.7 years. Persons with high tHcy (the fourth quartile) had more than twice as high a risk of developing AD than persons with low tHcy, even after adjusting for confounding or mediating factors. The third quartile of holo-TC was associated with a reduced risk of AD, after adjusting for Hcy and other confounders. CONCLUSIONS: These results suggest that Hcy is involved in the development of dementia and AD. The role of holo-TC was less clear and this marker needs to be studied further.
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| 30. |
- Kraemer, B. K., et al.
(författare)
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Efficacy of Prolonged- and Immediate-release Tacrolimus in Kidney Transplantation : A Pooled Analysis of Two Large, Randomized, Controlled Trials
- 2017
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Ingår i: Transplantation Proceedings. - : Elsevier BV. - 0041-1345 .- 1873-2623. ; 49:9, s. 2040-2049
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Tidskriftsartikel (refereegranskat)abstract
- Background. Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). Methods. Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, SCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). Results. Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). Conclusions. Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation.
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| 31. |
- Köhncke, Ylva, et al.
(författare)
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Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 181, s. 605-616
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Tidskriftsartikel (refereegranskat)abstract
- Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.
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| 32. |
- Laukka, Erika J, 1986-, et al.
(författare)
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Olfactory impairment and domain‐specific cognitive decline : A 12‐year population‐based study
- 2023
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Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 19:S18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Olfactory impairment has been associated with both cognitive impairment and dementia and Alzheimer’s disease (AD). This study aimed to investigate the association between olfactory dysfunction (OD) and change trajectories in different cognitive domains in aging. Method: Participants (n = 2473, mean age = 72 years, 61% female) from the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K) were repeatedly assessed with tasks measuring episodic memory, semantic memory, verbal fluency, and perceptual speed across 12 years. OD was measured at baseline and participants were categorized as normosmic, hyposmic, or anosmic based on the Sniffin’ Sticks odor identification task. Linear mixed-effects models were used to assess the associations between baseline OD and rates of cognitive decline. Result: OD was related to poorer baseline performance and faster rates of decline during follow-up in all examined domains, as well as in global cognition. Associations were generally more pronounced for anosmia compared to hyposmia. Conclusion: Olfactory impairment is associated with accelerated decline in aging across a wide range of cognitive domains.
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| 33. |
- Laukka, Erika J., et al.
(författare)
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Preclinical Cognitive Trajectories Differ for Alzheimer's Disease and Vascular Dementia
- 2012
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Ingår i: Journal of the International Neuropsychological Society. - 1355-6177 .- 1469-7661. ; 18:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- We investigated differences between Alzheimer's disease (AD) and vascular dementia (VaD) from the appearance of the first cognitive symptoms, focusing on both time of onset and rate of accelerated decline for different cognitive functions before dementia diagnosis. Data from a longitudinal population-based study were used, including 914 participants (mean age = 82.0 years, SD = 5.0) tested with a cognitive battery (word recall and recognition, Block Design, category fluency, clock reading) on up to four occasions spanning 10 years. We fit a series of linear mixed effects models with a change point to the cognitive data, contrasting each dementia group to a control group. Significant age-related decline was observed for all five cognitive tasks. Relative to time of diagnosis, the preclinical AD persons deviated from the normal aging curve earlier (up to 9 years) compared to the preclinical VaD persons (up to 6 years). However, once the preclinical VaD persons started to decline, they deteriorated at a faster rate than the preclinical AD persons. The results have important implications for identifying the two dementia disorders at an early stage and for selecting cognitive tasks to evaluate treatment effects for persons at risk of developing AD and VaD.
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| 34. |
- Lövdén, Martin, et al.
(författare)
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Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine-Cognition Associations
- 2018
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:11, s. 3894-3907
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with C-11-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed). Generally, greater receptor availability was associated with better cognitive performance. However, we discovered a subgroup of individuals for which high availability, particularly in striatum, was associated with poor performance, especially for working memory. Relative to the rest of the sample, this subgroup also had lower education, higher body-mass index, and lower resting-state connectivity between caudate nucleus and dorsolateral prefrontal cortex. We conclude that a smaller subset of individuals induces a multivariate non-linear association between dopamine D2/3R availability and cognitive performance in this group of older adults, and discuss potential reasons for these differences that await further empirical scrutiny.
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| 35. |
- MacDonald, Stuart W S, et al.
(författare)
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Extrastriatal dopamine D2 receptor binding modulates intraindividual variability in episodic recognition and executive functioning.
- 2009
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 47:11, s. 2299-2304
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Tidskriftsartikel (refereegranskat)abstract
- Intraindividual variability (IIV) reflects lawful but transient within-person changes in performance. Increased IIV in cognition shares systematic associations with numerous conditions characterized by alterations in dopamine (DA) neuromodulation (e.g., old age, ADHD, schizophrenia, and Parkinson's disease). In a group of normal middle-aged adults, we examined links between PET-derived measures of D2 receptor binding in striatum, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus (HC) and IIV for tasks assessing recognition memory and executive functioning. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful response latency trials for each cognitive outcome. Lower D2 binding in OC, ACC, and HC, but not striatum, was associated with increasing ISDs for the memory and executive measures. Consistent with neurocomputational models, the present findings suggest a role for extrastriatal DA neurotransmission in modulating variability in cognitive functioning.
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| 36. |
- MacDonald, Stuart W S, et al.
(författare)
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Intra-individual variability in behavior : links to brain structure, neurotransmission and neuronal activity.
- 2006
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Ingår i: Trends in Neurosciences. - : Elsevier BV. - 0166-2236. ; 29:8, s. 474-80
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Intra-individual variability reflects a transient, within-person change in behavioral performance. It is a common component of aging-related cognitive decline and the behavioral changes associated with neurodegenerative and other brain-related disorders such as traumatic brain injury and schizophrenia. Behavioral changes within an individual can reflect alterations at a systems or a cellular level in the brain, and monitoring intra-individual variability can therefore provide a warning of underlying pathology. Despite frequent reports of intra-individual variability, there is little synthesis, and no direct examination of the neural underpinnings. Here, we integrate seminal findings from cognitive research across lifespans of individuals, and also neuropsychological and neurobiological findings, to identify key questions and some potential answers, and to set challenges for fostering future research into intra-individual variability.
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| 37. |
- MacDonald, Stuart W S, et al.
(författare)
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Trajectories of cognitive decline following dementia onset : what accounts for variation in progression?
- 2011
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : Karger. - 1420-8008 .- 1421-9824. ; 31:3, s. 202-209
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified.METHODS: Cognitive change was examined for incident dementia cases (mild: n = 156; moderate: n = 77; severe: n = 73) and controls (n = 249) from the Kungsholmen Project, a community-based study of adults 75 years and older.RESULTS: For those with dementia, total variance attributed to between-person differences in cognitive decline was modest and linked to but a single predictor (history of cardiovascular disease). Although less variance in cognitive decline was observed for the similarly aged controls, numerous significant predictors of these differences were identified.CONCLUSION: The neurodegenerative process underlying dementia overshadows formerly significant predictors of cognitive change.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Rasmussen, Gunlög, et al.
(författare)
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Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteremia
- 2019
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Ingår i: Microbiology and immunology. - : Wiley-Blackwell Publishing Inc.. - 0385-5600 .- 1348-0421. ; 63:12, s. 487-499
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Tidskriftsartikel (refereegranskat)abstract
- The inflammasome is a multiprotein complex that mediates caspase-1 activation with subsequent maturation of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. The present study therefore aimed to investigate NLRP3 inflammasome activity in 20 S. aureus bacteremia patients, by repeated measurement during the first week of bacteremia, compared with controls. Caspase-1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (Fluorescent Labelled Inhibitor of Caspase-1), while IL-1β and IL-18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, mRNA expression of NLRP3, CASP1 (pro-caspase-1) and IL1B (pro-IL-1β) was analyzed by qPCR. We found induced caspase-1 activity in innate immune cells with subsequent release of IL-18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial inter-individual variation in caspase-1 activity between S. aureus bacteremia patients. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in S. aureus bacteremia could provide support in the effort to optimize management and treatment of each individual patient.
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| 42. |
- Shore, R. C., et al.
(författare)
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The Structure and Composition of Deciduous Enamel Affected by Local Hypoplastic Autosomal Dominant Amelogenesis Imperfecta Resulting from an ENAM Mutation
- 2010
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Ingår i: Cells Tissues Organs. - : S. Karger. - 1422-6405 .- 1422-6421. ; 191:4, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- In a group of families in northern Sweden, a mutation in the ENAM gene (predicted to produce a highly truncated protein) results in the local hypoplastic form of autosomal dominant amelogenesis imperfecta. In this study, sections of deciduous teeth from members of 3 of these families were examined by scanning electron microscopy (SEM) and the enamel mineral was analysed by energy dispersive X-ray spectroscopy (EDX). The sections were also probed with antibodies raised to a conserved sequence of the enamelin protein. Selected intact teeth were first analysed by digital imaging and ascribed with an 'Enamel Defects Index' (EDI) score. SEM of tooth sections revealed disrupted prism morphology and the prisms had a glass-like appearance in some areas. These areas of dysplasia were sometimes irregular but formed regular arrays in others. Comparison of EDI scores with SEM indicated that in one tooth the surface had no measurable defects but significant defects were present in the underlying enamel microstructure. SEM immunohistochemistry with the antibody raised to a fragment of the enamelin protein produced positive, but light, labelling throughout normal enamel. In dysplastic areas, however, the labelling intensity appeared to be reduced. The results indicate that the presence of functional enamelin in the correct amounts is necessary for correct prism morphogenesis. In addition, a combination of EDI and structural analysis indicate that defects in enamel microstructure are not necessarily visible as defects on the surface of the tooth, suggesting the possibility, at least, that some instances of under-diagnosis may occur. Copyright (C) 2009 S. Karger AG, Basel
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| 43. |
- Tufveson, G, et al.
(författare)
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Organ transplantation in Göteborg with particular reference to kidney transplantation.
- 1993
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Ingår i: Clinical transplants. - 0890-9016. ; , s. 243-51
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Tidskriftsartikel (refereegranskat)abstract
- The limiting factor in organ transplantation is the availability of organs. Continuing work to improve the public's willingness to donate organs and inspire hospital staff to collaborate in organ procurement is essential. Identification of patients who will not benefit from transplantation can also increase the availability of organs. Grafts may also be saved by identification and appropriate treatment of recurrent renal disease. Xenotransplantation may eventually solve the problem, but major obstacles remain. Meanwhile, work in this field may help to clarify mechanisms of rejection. New immunosuppressive drugs may improve graft survival and reduce the incidence and progression of chronic rejection.
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