| 1. |
- Wahlin, Bengt, et al.
(author)
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Osteoprotegerin and osteocalcin are associated with atherosclerosis in patients with rheumatoid arthritis : a prospective cohort study
- 2021
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In: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 39:6, s. 1402-1409
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Journal article (peer-reviewed)abstract
- OBJECTIVES:Patients with rheumatoid arthritis (RA) have an accelerated progression of atherosclerosis. The aim of this study was to examine the associations between subclinical atherosclerosis, assessed by intima-media thickness (IMT), and regulators of bone formation, markers of bone turnover and bone mineral density (BMD) in patients with RA.METHODS:Patients with new-onset RA (n=79), aged ≤60 years at diagnosis, were consecutively included in a study of development of atherosclerosis. Ultrasound measurement of IMT of the common carotid artery was undertaken at inclusion (T0) and after 11 years (T11) (n=54). Bone turnover biomarkers were examined in samples collected at T0 and T11. BMD was assessed at T11.RESULTS:In patients with RA, osteocalcin (OCN) and osteoprotegerin (OPG) measured at T11 were significantly associated with IMT at T11, adjusted for systolic blood pressure (SBP) and age. BMD at T11 and the bone turnover markers procollagen type 1 N-terminal propeptide (P1NP) and carboxy-terminal crosslinked C-terminal telopeptide (CTX) were not associated with IMT. OPG, OCN and sclerostin at T0 were significantly associated with IMT at T11, and OPG and OCN at T0 were associated with change in IMT from T0 to T11. The associations between IMT and bone biomarkers were stronger in patients with joint erosions at onset of RA, than in patients with non-erosive disease.CONCLUSIONS:Atherosclerosis in patients with RA is associated with OPG and OCN, but not with BMD or markers reflecting ongoing bone turnover, indicating that atherosclerosis is not associated with bone turnover per se.
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| 2. |
- Arndt, D. S., et al.
(author)
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State of the Climate in 2016
- 2017
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Journal article (peer-reviewed)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 3. |
- Cesaro, Simone, et al.
(author)
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Retrospective survey on the prevalence and outcome of prior autoimmune diseases in patients with aplastic anemia reported to the registry of the European group for blood and marrow transplantation.
- 2010
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In: Acta Haematologica. - : Karger. - 0001-5792 .- 1421-9662. ; 124:1, s. 19-22
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Journal article (peer-reviewed)abstract
- BACKGROUND: Aplastic anemia (AA) is rarely described after a diagnosis of autoimmune disease (aID). AIMS: To assess the prevalence of prior aID in patients with AA recorded in the registry of the European Group for Blood and Marrow Transplantation (EBMT) and to evaluate treatment and outcome. METHODS: 1,251 AA patients from 18 EBMT centers were assessed. RESULTS: Fifty patients (4%) were eligible: 22 males and 28 females with a median age of 46 years at the diagnosis of aID and of 51 years at the diagnosis of AA. Information on the treatment of AA was available in 49 patients: 38 received only immunosuppressive therapy (IST), 8 patients underwent hematopoietic stem cell transplantation (HSCT) - 6 as first-line therapy and 2 after failure of IST - whilst 3 patients had a spontaneous recovery. After a median follow-up of 3.19 years, 32 patients were alive, including 7 of the 8 patients who underwent HSCT. Only 6 of 32 patients who were alive at the last follow-up were receiving IST for AA. CONCLUSIONS: Most cases of AA following aID benefitted from IST or HSCT if a matched donor was available. Further prospective investigation is needed to assess the effects of IST on the outcome of underlying aID.
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| 4. |
- Dahl, Anna, 1975-
(author)
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Body mass index, cognitive ability, and dementia : prospective associations and methodological issues in late life
- 2009
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Doctoral thesis (other academic/artistic)abstract
- The aims of the present study were to investigate the association between overweight and cognitive ability and dementia, and to evaluate the usefulness of self-reported body mass index (BMI) in late life and various data sources commonly used in epidemiological studies to identify persons with dementia. Data were drawn from three population-based studies: the Swedish Adoption/Twin Study of Aging (SATSA), Aging in Women and Men: A Longitudinal Study of Gender Differences in Health Behaviour and Health among Elderly (the Gender Study), and the Finnish Lieto Study. In Study I, the agreement between self-reported and measured BMI over time was evaluated among 774 men and women, ages 40 to 88 years at baseline (mean age 63.9) participating in both the questionnaire phase and in-person testing of SATSA. Latent growth curve (LGC) modeling showed a small but significant increase between self-reported and measured BMI (0.02 kg/m2/y) over time, which would probably not affect the results if self-reported BMI were used as a continuous variable in longitudinal research. In Study II, the agreement between dementia diagnoses from various sources and dementia diagnoses set at a consensus conference was evaluated. Among the 498 elderly people ages 70 to 81 at baseline (mean age 74.5) enrolled in the Gender Study, 87 were diagnosed with dementia during an eight-year period. Review of medical records and nurse evaluations yielded the highest sensitivity (0.83 and 0.80, respectively) and a high specificity (0.98 and 0.96), indicating that these sources might be good proxies of dementia, while data extraction from the Swedish Inpatient Discharge Registry underestimated the prevalence of dementia (sensitivity 0.26). In Study III, the association between being overweight in midlife and cognitive ability in late life was examined in SATSA. The 781 participants ages 25 to 63 at baseline (mean age 41.6) in 1963 or 1973 self-reported their height and weight. From 1986 until 2002, they were assessed five times using a cognitive test battery. LGC models showed that people with higher midlife BMI scores had significantly lower cognitive ability and a significantly steeper decline than their thinner counterparts, an association that persisted when those who developed dementia during the study period were excluded from the analysis. This finding indicates that being overweight might affect cognitive ability independently of dementia. In Study IV, the association between BMI and dementia risk in older persons was described among 605 persons without dementia and ages 65 to 92 at baseline (mean age 70.8) in the Lieto Study. Among these, 86 persons were diagnosed with dementia during eight years of follow-up. Cox regression analyses indicated that for each unit increase in BMI score, the risk of dementia decreased 8% (hazard ratio = 0.92, 95% confidence interval = 0.87–0.97) and the association remained significant when individuals who developed dementia during the first four years of follow-up were excluded from the analyses. This result suggests that low BMI scores are present almost a decade before clinical dementia onset.
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| 5. |
- Dijken, Jan W.V. van, 1947-, et al.
(author)
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Samarbete breddar forskning : Oral Biomaterialgruppen, Umeå
- 2008
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In: Tandläkartidningen. - : Sveriges Tandläkarförbund. ; 100:5, s. 74-79
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Journal article (pop. science, debate, etc.)abstract
- Vid institutionen för odontologi vid Umeå Universitet finns en lång tradition av biomaterialforskning. För drygt två år sedan samlades större delen av den forskningen i ett vetenskapligt nätverk. Här beskrivs ett axplock av det breda forskningsarbetet.
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| 6. |
- Hofstedt, Oscar E., et al.
(author)
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Associations between serological biomarkers and subclinical atherosclerosis in patients with rheumatoid arthritis after 11 years of follow-up
- 2024
-
In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 42:5, s. 967-973
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the relationship between biomarkers known to be involved in both chronic inflammation and subclinical atherosclerosis, as measured by carotid intima media thickness (cIMT), in patients with RA compared to controls.METHODS: Between 2000 and 2004, all patients under 60 years of age with newly diagnosed RA in the northern region of Sweden were invited to participate in this study. Measurements of cIMT were undertaken at inclusion (T0), after five years of follow-up (T5) and after eleven years of follow-up (T11). Patients were clinically assessed and blood was drawn for analysis of biomarkers.RESULTS: In patients with RA (n=54), linear regression models showed that cIMT at T11 was associated with levels of GDF-15 at T5 and T11, but not with baseline levels. GDF-15 was strongly associated with age. At T11, mean level of GDF-15 was elevated compared to controls. Levels of adiponectin, MCP-1, cathepsin S, endoglin and IL-6 were higher in patients with RA compared to controls, but showed no association with cIMT. In multivariable linear regression models with cIMT at T11 as dependent variable, change in GDF-15 from T0 to T11 was associated to an increase in cIMT at T11. Adjusting for systolic blood pressure and age respectively rendered this association statistically non-significant,CONCLUSIONS: Among these patients with RA GDF-15 was associated to cIMT after 11 years of follow-up. GDF-15 should be a biomarker of interest in future research, to further understand its role in the accelerated atherogenesis in patients with RA.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Korlén, S., et al.
(author)
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Managerial strategies to make incentives meaningful and motivating
- 2017
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In: Journal of Health Organization & Management. - : Emerald Group Publishing Ltd.. - 1477-7266 .- 1758-7247. ; 31:2, s. 126-141
-
Journal article (peer-reviewed)abstract
- Purpose: Policy makers are applying market-inspired competition and financial incentives to drive efficiency in healthcare. However, a lack of knowledge exists about the process whereby incentives are filtered through organizations to influence staff motivation, and the key role of managers is often overlooked. The purpose of this paper is to explore the strategies managers use as intermediaries between financial incentives and the individual motivation of staff. The authors use empirical data from a local case in Swedish specialized care. Design/methodology/approach: The authors conducted an exploratory qualitative case study of a patient-choice reform, including financial incentives, in specialized orthopedics in Sweden. In total, 17 interviews were conducted with professionals in managerial positions, representing six healthcare providers. A hypo-deductive, thematic approach was used to analyze the data. Findings: The results show that managers applied alignment strategies to make the incentive model motivating for staff. The managers’ strategies are characterized by attempts to align external rewards with professional values based on their contextual and practical knowledge. Managers occasionally overruled the financial logic of the model to safeguard patient needs and expressed an interest in having a closer dialogue with policy makers about improvements. Originality/value: Externally imposed incentives do not automatically motivate healthcare staff. Managers in healthcare play key roles as intermediaries by aligning external rewards with professional values. Managers’ multiple perspectives on healthcare practices and professional culture can also be utilized to improve policy and as a source of knowledge in partnership with policy makers.
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| 11. |
- Liljeholm, Maria, et al.
(author)
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Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23
- 2013
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In: Blood. - Washington : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:23, s. 4791-4799
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Journal article (peer-reviewed)abstract
- Haplotype analysis and targeted next-generation resequencing allowed us to identify a mutation in the KIF23 gene and to show its association with an autosomal dominant form of congenital dyserythropoietic anemia type III (CDA III). The region at 15q23 where CDA III was mapped in a large Swedish family was targeted by array-based sequence capture in a female diagnosed with CDA III and her healthy sister. Prioritization of all detected sequence changes revealed 10 variants unique for the CDA III patient. Among those variants, a novel mutation c.2747C>G (p.P916R) was found in KIF23, which encodes mitotic kinesin-like protein 1 (MKLP1). This variant segregates with CDA III in the Swedish and American families but was not found in 356 control individuals. RNA expression of the 2 known splice isoforms of KIF23 as well as a novel one lacking the exons 17 and 18 was detected in a broad range of human tissues. RNA interference-based knock-down and rescue experiments demonstrated that the p.P916R mutation causes cytokinesis failure in HeLa cells, consistent with appearance of large multinucleated erythroblasts in CDA III patients. We conclude that CDA III is caused by a mutation in KIF23/MKLP1, a conserved mitotic kinesin crucial for cytokinesis.
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| 12. |
- Mei, Ya-Fang, et al.
(author)
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Human hematopoietic (CD34+) stem cells possess high-affinity receptors for adenovirus type 11p
- 2004
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In: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 328:2, s. 198-207
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Journal article (peer-reviewed)abstract
- Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.
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| 13. |
- Moradi, Shahram, et al.
(author)
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The Efficacy of Short-term Gated Audiovisual Speech Training for Improving Auditory Sentence Identification in Noise in Elderly Hearing Aid Users
- 2017
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In: Frontiers in Psychology. - : FRONTIERS MEDIA SA. - 1664-1078. ; 8
-
Journal article (peer-reviewed)abstract
- This study aimed to examine the efficacy and maintenance of short-term (one-session) gated audiovisual speech training for improving auditory sentence identification in noise in experienced elderly hearing-aid users. Twenty-five hearing aid users (16 men and 9 women), with an average age of 70.8 years, were randomly divided into an experimental (audiovisual training, n = 14) and a control (auditory training, n = 11) group. Participants underwent gated speech identification tasks comprising Swedish consonants and words presented at 65 dB sound pressure level with a 0 dB signal-to-noise ratio (steady-state broadband noise), in audiovisual or auditory-only training conditions. The Hearing-in-Noise Test was employed to measure participants auditory sentence identification in noise before the training (pre-test), promptly after training (post-test), and 1 month after training (one-month follow-up). The results showed that audiovisual training improved auditory sentence identification in noise promptly after the training (post-test vs. pre-test scores); furthermore, this improvement was maintained 1 month after the training (one-month follow-up vs. pre-test scores). Such improvement was not observed in the control group, neither promptly after the training nor at the one-month follow-up. However, no significant between-groups difference nor an interaction between groups and session was observed. Conclusion: Audiovisual training may be considered in aural rehabilitation of hearing aid users to improve listening capabilities in noisy conditions. However, the lack of a significant between-groups effect (audiovisual vs. auditory) or an interaction between group and session calls for further research.
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| 14. |
- Newman, Louise, et al.
(author)
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Delivering sustained, coordinated and integrated observations of the Southern Ocean for global impact
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Research review (peer-reviewed)abstract
- The Southern Ocean is disproportionately important in its effect on the Earth system, impacting climatic, biogeochemical and ecological systems, which makes recent observed changes to this system cause for global concern. The enhanced understanding and improvements in predictive skill needed for understanding and projecting future states of the Southern Ocean require sustained observations. Over the last decade, the Southern Ocean Observing System (SOOS) has established networks for enhancing regional coordination and research community groups to advance development of observing system capabilities. These networks support delivery of the SOOS 20-year vision, which is to develop a circumpolar system that ensures time series of key variables, and deliver the greatest impact from data to all key end-users. Although the Southern Ocean remains one of the least-observed ocean regions, enhanced international coordination and advances in autonomous platforms have resulted in progress towards addressing the need for sustained observations of this region. Since 2009, the Southern Ocean community has deployed over 5700 observational platforms south of 40°S. Large-scale, multi-year or sustained, multidisciplinary efforts have been supported and are now delivering observations of essential variables at space and time scales that enable assessment of changes being observed in Southern Ocean systems. The improved observational coverage, however, is predominantly for the open ocean, encompasses the summer, consists of primarily physical oceanographic variables and covers surface to 2000 m. Significant gaps remain in observations of the ice-impacted ocean, the sea ice, depths more than 2000 m, the air-sea-ice interface, biogeochemical and biological variables, and for seasons other than summer. Addressing these data gaps in a sustained way requires parallel advances in coordination networks, cyberinfrastructure and data management tools, observational platform and sensor technology, platform interrogation and data-transmission technologies, modeling frameworks, and internationally agreed sampling requirements of key variables. This paper presents a community statement on the major scientific and observational progress of the last decade, and importantly, an assessment of key priorities for the coming decade, towards achieving the SOOS vision and delivering essential data to all end users.
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| 15. |
- Pedersen, Robin, et al.
(author)
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When functional blurring becomes deleterious : Reduced system segregation is associated with less white matter integrity and cognitive decline in aging
- 2021
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 242
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Journal article (peer-reviewed)abstract
- Healthy aging is accompanied by progressive decline in cognitive performance and concomitant changes in brain structure and functional architecture. Age-accompanied alterations in brain function have been characterized on a network level as weaker functional connections within brain networks along with stronger interactions between networks. This phenomenon has been described as age-related differences in functional network segregation. It has been suggested that functional networks related to associative processes are particularly sensitive to age-related deterioration in segregation, possibly related to cognitive decline in aging. However, there have been only a few longitudinal studies with inconclusive results. Here, we used a large longitudinal sample of 284 participants between 25 to 80 years of age at baseline, with cognitive and neuroimaging data collected at up to three time points over a 10-year period. We investigated age-related changes in functional segregation among two large-scale systems comprising associative and sensorimotor-related resting-state networks. We found that functional segregation of associative systems declines in aging with exacerbated deterioration from the late fifties. Changes in associative segregation were positively associated with changes in global cognitive ability, suggesting that decreased segregation has negative consequences for domain-general cognitive functions. Age-related changes in system segregation were partly accounted for by changes in white matter integrity, but white matter integrity only weakly influenced the association between segregation and cognition. Together, these novel findings suggest a cascade where reduced white-matter integrity leads to less distinctive functional systems which in turn contributes to cognitive decline in aging.
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| 16. |
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| 17. |
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| 18. |
- Sundström, Gunnel, et al.
(author)
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Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.
- 2005
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In: Medical Oncology. - 1357-0560 .- 1559-131X. ; 22:1, s. 71-78
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Journal article (peer-reviewed)abstract
- The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC α-cardiac. The expression of MyHC α-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaing MyHC isoforms were generelly not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.
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| 19. |
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| 20. |
- Sundström, Gunnel, 1940-
(author)
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Hyaluronan in normal and malignant bone marrow : a clinical and morphological study with emphasis on myelofibrosis
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Fibrosis in the bone marrow is usually denominated myelofibrosis and may contribute to impaired hematopoiesis. Myelofibrosis is seen both in malignant and non-malignant diseases. The normal microenvironment in the bone marrow consists of a heterogenous population of hematopoietic and non-hematopoietic stromal cells, their extracellular products and hematopoietic cytokines. The stromal cells produce a complex array of molecules, among others collagens and glycosaminoglycans (GAGs) of which hyaluronan (HYA) is the most abundant. Marrow fibrosis results from an increased deposition of collagens, which are polypeptides. Staining for reticulin, mostly composed of collagen type III, is the common way of visualizing myelofibrosis. HYA, like the collagens, is widely distributed in connective tissues. Little is known about the distribution of HYA in bone marrow. The aims of this thesis have been to determine how HYA is distributed in normal and malignant bone marrow, compared to reticulin staining, and to follow patients with chronic myeloproliferative diseases (CMPD) during two years treatment with anagrelide considering development of cellularity and fibrosis. In bone marrow biopsies from healthy volunteers, the controls, HYA was found in a pattern that was concordant with the reticulin staining. Comparing patients with different malignant diseases with and without bone marrow involvemen, HYA staining was found to be significantly stronger in both groups compared to the controls. The HYA scores were also significantly higher in the bone marrow of patients with de novo acute myeloid leukemia (AML), compared to the controls. There was a correlation between HYA and reticulin in the patients with de novo AML, and in the patients with different malignant diseases with and without bone marrow involvement as in the controls. Increase of HYA, reticulin and cellularity in the bone marrow of patients with CMPD after two years of treatment with anagrelide indicated progression of fibrosis. Anagrelide is a valuable drug for reduction of platelets but seems unable to stop progression of fibrosis and hypercellularity. HYA is an interesting molecule with properties not only contributing to the structure of extracellular matrix but also to cell signaling and behaviour, although the understanding of the detailed mechanisms is still incomplete.
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| 21. |
- Thunström Salzer, Anna, et al.
(author)
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Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients
- 2018
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 9
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Journal article (peer-reviewed)abstract
- Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors. Still, the actual functionality of neutrophils resulting from G-CSF treatment remains insufficiently understood. We tested the ex vivo functionality of neutrophils isolated from blood of G-CSF-treated healthy SC donors. We quantified chemotaxis, oxidative burst, and phagocytosis before and after treatment and detected significantly reduced chemotactic activity upon G-CSF treatment. Similarly, in vitro treatment of previously untreated neutrophils with G-CSF led to reduced chemotactic activity. In addition, we revealed that this effect persists in the allogeneic SC recipients up to 4 weeks after neutrophil engraftment. Our data indicates that neutrophil quantity, as a sole measure of immunocompetence in high-risk patients should be considered cautiously as neutrophil functionality might be affected by the primary treatment.
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| 22. |
- Wahlin, Bengt, et al.
(author)
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Atherosclerosis in rheumatoid arthritis : associations between anti-cytomegalovirus IgG antibodies, CD4+CD28null T-cells, CD8+CD28null T-cells and intima-media thickness
- 2021
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology S.A.S.. - 0392-856X .- 1593-098X. ; 39:3, s. 578-586
-
Journal article (peer-reviewed)abstract
- Objectives: Patients with rheumatoid arthritis (RA) have an accelerated progression of atherosclerosis. The aims of this study were to study the associations between subsets of T-cells, subclinical atherosclerosis assessed by intima-media thickness (IMT) and serological status for CMV in patients with RA.Methods: Patients with new-onset RA (n=79), aged ≤60 years at diagnosis, were included in a prospective study of atherosclerosis. Controls matched for age and sex were also included (n=44). Ultrasound measurement of IMT in the common carotid artery was undertaken at inclusion (T0), after 1.5 years (T1.5) and after 11 years (T11). At T11, flow-cytometry analysis was undertaken to investigate subsets of T-cells. Serological analysis for CMV was undertaken from samples collected at T0.Results: At T0, 66% of the patients and controls were CMV immunoglobulin G-positive. CMV-IgG positive patients had a significantly more rapid increase in IMT at T1.5, compared with controls and CMV-IgG negative patients. CMV-IgG positive patients had a significantly higher percentage of T-cells lacking CD28 (both CD4+CD28null and CD8+CD28null T-cells) than CMV-IgG negative patients. Increased levels of CD4+CD28null and CD8+CD28null T-cells were significantly associated with IMT at T11, adjusted for systolic blood pressure. CX3CR1 was expressed in CD4+ and CD8+ CD28null T-cells, but CX3CR1 per se was not associated with increased IMT.Conclusions: Presence of CMV IgG-antibodies in patients with RA is associated with altered T-cell-populations and an increased burden of atherosclerosis. A possible protective effect of antiviral treatment in CMV-positive patients with new-onset RA should be considered.
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| 23. |
- Wahlin, Bengt, 1977-
(author)
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Atherosclerotic cardiovascular disease in rheumatoid arthritis : aspects of pathogenesis and risk
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Patients with rheumatoid arthritis (RA) have an increased prevalence and severity of atherosclerosis, and a corresponding increased risk of cardiovascular disease. The mechanisms causing this are not well elucidated, but both traditional cardiovascular risk factors and RA-associated factors have been associated with atherosclerosis and increased risk of cardiovascular events in patients with RA. Cardiovascular risk estimation based on traditional cardiovascular risk factors, often underestimates the risk in patients with RA. The aims of this thesis were to examine factors and biomarkers associated with atherosclerosis in patients with RA, and to evaluate an algorithm for cardiovascular risk estimation in patients with RA.Methods Patients with early RA in the four northernmost counties of Sweden have since 1995 been included in a prospective study of both the progress of RA and comorbidities. Besides clinical data, radiographs, genetic markers and autoantibodies are registered. Paper I includes 665 patients aged 40-80 years from that cohort, in whom the 10-year risk of a first cardiovascular event was estimated with both Expanded Cardiovascular Risk Prediction Score in Rheumatoid Arthritis (ERS-RA), and the general population based ACC/AHA algorithm. The estimations were then compared to the actual outcomes. Paper II examines factors associated with coronary artery calcification (CAC) in 22 patients with long-standing RA. Papers III and IV use data from a cohort of patients <60 years of age at diagnosis of RA (n=79), in whom development of atherosclerosis has been prospectively followed since diagnosis of RA. This is a subset of patients from the larger cohort in paper I. Controls matched for age and sex (n=44) are examined as well. In paper III, phenotypes of T-cells and IgG-antibodies against cytomegalovirus (CMV) are analysed in relation to carotid intima-media thickness (IMT). In paper IV, bone mineral density and markers and regulators of bone metabolism are analysed in relation to IMT.Results Cardiovascular risk estimation with the RA-specific algorithm ERS-RA is not superior to estimation with the ACC/AHA algorithm. Both algorithms underestimate the risk in patients with a high grade of inflammation and in patients with an estimated moderate risk. In patients with long-standing RA, presence of CAC is associated with inflammatory activity, both at time of examination and in earlier stages of RA. Presence of anti-CMV IgG antibodies and altered T-cells (both CD4+ and CD8+) lacking the co-stimulatory molecule CD28 (CD28null) are associated with a higher IMT, and patients IgG-positive for CMV have a rapid increase in IMT after onset of RA. Regulators of bone metabolism (sclerostin, osteoprotegerin and osteocalcin) are associated with a higher IMT in patients with RA.Conclusion Cardiovascular risk estimation in patients with RA still needs to be improved. The fact that CMV-positivity, altered populations of T-cells and IMT all are associated, and that also regulators of bone metabolism reflect IMT, suggests that the pathogenesis of atherosclerosis in patients with RA is multifactorial. This thesis provides knowledge of the accelerated development of atherosclerosis in RA and could possibly be relevant also in other chronic inflammatory diseases, where markers of accelerated atherosclerosis and increased cardiovascular risk are lacking.
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