| 1. |
- Nyberg, Lars, et al.
(författare)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:52, s. 22682-22686
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 2. |
- Salami, Alireza, et al.
(författare)
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Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition
- 2012
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Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier. - 0925-4439 .- 1879-260X. ; 1822:3, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest. WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
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| 3. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 4. |
- Giddaluru, Sudheer, et al.
(författare)
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Genetics of structural connectivity and information processing in the brain
- 2016
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Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 221:9, s. 4643-4661
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
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| 5. |
- Xin, D. L., et al.
(författare)
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Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task
- 2017
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Ingår i: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.
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| 6. |
- Hall, Håkan, et al.
(författare)
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In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting
- 2012
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Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - 2160-8407. ; 2:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with (67)Ga or (68)Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of (67/68)Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using (67)Ga and SPECT or (68)Ga and PET.
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| 7. |
- Holmboe, Michael
(författare)
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The bentonite barrier : microstructural aspects on colloid filtration and radiation effects on bentonite colloid stability
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In many countries a multi-barrier concept in a deep geological repository is planned for final disposal of nuclear waste. Many of these different concepts, for example the Swedish KBS-3 model, include an engineered barrier consisting of compacted bentonite. The compacted bentonite barrier will be positioned around copper canisters holding the nuclear waste and act as a transport barrier for various radioactive species. This is due to the compact microstructure as well as the large sorption capacity of compacted water saturated bentonite. During its required lifetime (> 100000 years) a deep geological repository and the bentonite barrier itself will be subjected to changing groundwater composition and flow, geochemistry, temperature, and large doses of ionizing irradiation. The long lifetime and significance of a deep geologic repository mean that it must be regarded as a thermodynamically open system and be assessed in terms of worst case scenarios. In case of water bearing fractures, formed by future movements in the granitic host bedrock, low ionic strength groundwater can endanger the stability of the bentonite barrier. Prolonged erosion of the bentonite barrier might cause significant loss of buffer material and jeopardize its overall functionality. This thesis deals with the microstructure of the water saturated compacted bentonite as a function of compaction, as well as effects of γ-radiation on bentonite dispersions. The microstructure was investigated both indirectly through colloid filtration experiments, as well as using low-angle XRD. Effects of γ-irradiation were investigated in terms of colloid stability and sediment behavior of bentonite (and Na-montmorillonite) dispersions. The colloid filtration experiments, using small gold colloids of different sizes as tracers, shows that the microstructural constraints of bentonite effectively filter even extremely small inorganic colloids. Colloid transport was only observed at very low compactions (i.e. dry density g/cm3) where the average interlayer distances of montmorillonite exceeded the colloid size, indicating interlayer rather than interparticle transport. From the low-angle XRD experiments the free porosity of water saturated compacted bentonite was determined by comparing its basal spacings (interlayer distances + 1 nm) with the hypothetical basal spacings assuming no free porosity. Irrespective of compaction, the maximum free porosity proved to be very low, in line with the colloid filtration experiments. The results showed that existing microstructural models sometimes exaggerate the importance of interparticle voids. The γ-irradiation experiments showed a radiation induced increase in colloid stability. This radiation induced effect also changed the sedimentation behavior of irradiated bentonite dispersions compared to unirradiated samples. The effect is attributed to an increase in surface potential of the bentonite colloids, due to reactions with the short-lived radicals formed upon water radiolysis.
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| 8. |
- Eriksson Sörman, Daniel, et al.
(författare)
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Social relationships and risk of dementia : a population-based study
- 2015
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 27:8, s. 1391-1399
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD).Methods: We studied 1,715 older adults (>= 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry.Results: We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD.Conclusions: The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.
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| 9. |
- Krupic, Ferid, et al.
(författare)
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Migrant general practitioners' experiences of using interpreters in health-care : a qualitative explorative study
- 2017
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Ingår i: Medicinski arhiv. - : ScopeMed. - 0350-199X .- 1986-5961. ; 71:1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: According to the UNHCR, 250 million people currently live outside their country of birth. The growing multicultural population poses a major challenge to healthcare professionals who aim to provide individualized, holistic care, which respects the individual's autonomy. To ensure basic rights, healthcare interventions should be guided by the value of benefiting others; individuals should be treated honestly, equally, and impartially.OBJECTIVE: To investigate immigrant doctors' experiences of using interpreters in the Swedish health-care system.MATERIAL AND METHODS: Twenty-eight doctors, 12 men and 16 women from Bosnia and Herzegovina, Croatia, Macedonia and Serbia participated in four focus group interviews (FGI). The interviews were audio recorded, transcribed and analyzed using content analysis method.RESULTS: The best results in the present study were achieved in situations where a professional interpreter was involved. In some cases, the doctors were forced to use relatives or a colleague to interpret, which in many cases proved to be a mistake. The consequences of poor interpretation routines included payment by mistake, a patient paying an interpreter who refused to interpret, time spent waiting for another interpreter, as well as disturbances to the daily work schedule. Finding someone who could replace an interpreter who did not show up caused time shortage and increased stress.CONCLUSIONS: Improved routines and more effective cooperation between interpreting services and health-care centers are needed in order to ensure that using professional interpreters guarantees appropriate, high quality care. Improvements are needed to provide satisfactory health-care to people with limited language skills. In order to achieve this, better education of interpreters is needed, especially regarding cultural diversity and medical terminology. These improvements present complex challenges, deserving empirical and critical reflection in order to improve the work situation for doctors.
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| 10. |
- Wanders, A., et al.
(författare)
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Abolition of the effect of cyclosporine on rat cardiac allograft rejection by the new immunomodulator LS-2616 (Linomide)
- 1989
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 47:2, s. 216-7
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the quinoline-3-carboxamide LS-2616 (Linomide), given alone or together with cyclosporine, was studied in the first set cardiac allograft transplantation model in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto rat recipients on day 0. The recipients were given LS-2616 orally on day -1 to rejection and/or CsA orally on days 0-9. In untreated animals rejection occurred on days 8-9, as judged by the absence of palpable pulsations. Treatment with CsA (5 or 10 mg/kg) resulted in prolongation of graft survival to days 17-21, i.e., the rejection occurred 8-10 days after cessation of treatment. LS-2616 in a dose of 160 mg/kg did not in itself have any impact on graft survival, but when given in doses of 40 or 160 mg/kg simultaneously with CsA (10 mg/kg), the effect of CsA was totally abolished. Animals treated with LS-2616 together with CsA had slightly lower trough blood levels than those treated with CsA alone. This interaction with CsA pharmacokinetics does not explain the results, as doubling of the CsA dose to 20 mg/kg, which well compensated for the difference in blood levels, was not sufficient to reverse the effect of LS-2616. To our knowledge this is the first compound known to abolish the effect of CsA. The mechanism is unknown, but is is possible that studies on the interaction between these two drugs will shed further light on the molecular basis of their modes of action.
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