| 1. |
- Ekman, Diana S, et al.
(författare)
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Is Sweden still a role model for safety? An overview of unintentional injury data over the past two decades
- 2010
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Ingår i: INTERNATIONAL JOURNAL OF INJURY CONTROL AND SAFETY PROMOTION. - : Taylor and Francis. - 1745-7300 .- 1745-7319. ; 17:3, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates injury-related mortality and hospitalisations, during 1987-2007 in Sweden. Injuries were classified according to International Classification of Diseases (ICD) -8 for pre-1987 injuries, ICD-9 for 1987-1996 injuries and ICD-10 for injuries occurring in 1997 and later. Data on mortality from injuries during 1987-2007 were collected from Swedens national Cause-of-Death Register, while data concerning injury diagnoses leading to hospitalisation stays of at least 24h, occurring during 1987-2007, were obtained from the national Patient Register. Crude rates were derived for injury-related deaths and injury-related hospitalisations for age-gender groups, using population data from Statistics Sweden. Our results showed a mixed picture of injury-related hospitalisations and deaths over the study period. Absolute numbers of injury-related deaths and injury-related hospitalisations decreased over time for the population as a whole and for many, but not all, age-gender groups. When assessing crude injury-related death rates and crude injury-related hospitalisation rates over time, as categorised by gender and age groupings, we also found unchanging or increased risks for injury-related deaths and/or hospitalisations for several age-gender groups. While Sweden has made remarkable progress in reducing injury-related deaths and hospitalisations, there are clear differences in risk that remain.
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| 2. |
- Ekman, Diana Stark, 1958-, et al.
(författare)
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Twenty-five years of bicycle helmet promotion for children in Skaraborg District, Sweden.
- 2012
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Ingår i: International Journal of Injury Control and Safety Promotion. - : Informa UK Limited. - 1745-7300 .- 1745-7319. ; 19:3, s. 213-217
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to describe some of the results of a long-term bicycle helmet campaign for children in Skaraborg District, Sweden. The hospital discharge data for bicycle-related injuries occurring in children under the age of 15 were reviewed, to assess changes in patterns for head and other body injuries. The study shows that head injuries to children as a result of bicycle injuries were reduced between 94 and 99% in the study areas. The tremendous gains in safety for children who ride bicycles in Skaraborg District were the result of not only national policy changes that occurred in the latter half of this study period but also the result of local collaborations based on the Safe Communities model, which were organised during the first part of the study period.
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| 3. |
- Ekman, Robert, et al.
(författare)
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A comparison of unintentional injury patterns occurring in two Swedish communities in 1978 and in 2008
- 2015
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Ingår i: International Journal of Injury Control and Safety Promotion. - : Taylor & Francis. - 1745-7300 .- 1745-7319. ; 22:3, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Surveillance and analyses of unintentional injuries can be used to help prioritise community prevention efforts. This study describes changes in local patterns for unintentional injuries resulting in deaths, hospitalisations, and outpatient visits to health care clinics and emergency rooms, comparing information from two different study periods, 1978 and 2008, in the Swedish communities of Falköping and Lidköping. Injury cases were analysed, and confidence intervals were derived. The study results show that while most injuries decreased comparing the first study period to the second, these changes were only significant in terms of decreases in outpatient care. This study points to the importance of more systematic collection data of injury events treated at the outpatient level, particularly for communities where there are relatively low numbers of injury-related deaths and hospitalisations.
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| 4. |
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| 5. |
- Nilsen, Per, et al.
(författare)
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Effectiveness of Community-Based Injury Prevention : Injury Rate Levels, Changes, and Trends for 14 Swedish WHO-Designated Safe Communities
- 2007
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Ingår i: Accident Analysis and Prevention. - : Elsevier BV. - 0001-4575 .- 1879-2057. ; 39:2, s. 267-273
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the injury rate levels, changes, and trends between 1987 and 2002 for the 14 Swedish municipalities designated as WHO Safe Communities. The injury rate was defined as the number of injured patients discharged from hospital per 1000 persons. Injury rates were age standardised. Each municipality was compared with its respective municipality group, according to a classification of Sweden's 288 municipalities into nine groups based on numerous structural parameters. The average injury rate levels for the 14 WHO-designated Safe Community municipalities ranged from 11.54 to 19.09 per 1000 population during the study period, which was defined as the time period during which a municipality's injury prevention program has been operational. Eleven of 14 municipalities had higher levels than their corresponding municipality groups. Five of the 14 municipalities “outperformed” their respective municipality groups and achieved a greater relative injury rate decrease during the study period. The trends for the 14 municipalities in relation to their municipality groups showed an inconsistent pattern, with only four municipalities exhibiting overall favourable trends for the study period.
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| 6. |
- Timpka, Toomas, 1957-, et al.
(författare)
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Community-level football injury epidemiology : traumatic injuries treated at Swedish emergency medical facilities
- 2018
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 28:1, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the popularity of the sport, few studies have investigated community-level football injury patterns. This study examines football injuries treated at emergency medical facilities using data from three Swedish counties.Methods: An open-cohort design was used based on residents aged 0-59 years in three Swedish counties (pop. 645 520). Data were collected from emergency medical facilities in the study counties between 1 January 2007 and 31 December 2010. Injury frequencies and proportions for age groups stratified by sex were calculated with 95% confidence intervals (95% CIs) and displayed per diagnostic group and body location.Results: Each year, more than 1/200 person aged 0-59 years sustained at least one injury during football play that required emergency medical care. The highest injury incidence was observed among adolescent boys [2009 injuries per 100 000 population years (95% CI 1914-2108)] and adolescent girls [1413 injuries per 100 000 population years (95% CI 1333-1498)]. For female adolescents and adults, knee joint/ligament injury was the outstanding injury type (20% in ages 13-17 years and 34% in ages 18-29 years). For children aged 7-12 years, more than half of the treated injuries involved the upper extremity; fractures constituted about one-third of these injuries.Conclusions: One of every 200 residents aged 0-59 years in typical Swedish counties each year sustained a traumatic football injury that required treatment in emergency healthcare. Further research on community-level patterns of overuse syndromes sustained by participation in football play is warranted.
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| 7. |
- Zare, Zahra, et al.
(författare)
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Cognitive Distortions as Trauma-Specific Irrational Beliefs Among Burn Patients
- 2019
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Ingår i: Journal of Burn Care & Research. - : Oxford University Press. - 1559-047X .- 1559-0488. ; 40:3, s. 361-367
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Tidskriftsartikel (refereegranskat)abstract
- Burn injuries are most certainly stressful events, particularly when permanent disfigurement is a result. This situation can lead to the onset of irrational beliefs which can in turn lead to long-term psychological problems such as depression, anxiety, shame, guilt, posttraumatic stress, etc. The objective of this study is to explore the irrational beliefs among burn patients and its correlates in an Iranian sample. This cross-sectional study included 329 patients who had experienced disfigurement, as result of burn injuries. In order to assess irrational beliefs, a Scale for Irrational Thoughts after Burning was used. To identify correlated variables with irrational beliefs, both bivariate and multivariate analysis methods were conducted. In multivariate linear regression, forward strategy was used for building the model. The results of bivariate analysis showed that the location of the burn on bodies (body parts generally exposed in social environment or parts culturally perceived as sensitive areas of body), marital status, urbanities, age group, geographical areas, etiology of burning, and intent of injury had significant relationships with irrational beliefs (P < .05). Using forward linear regression, gender, marital status, geographical areas, etiology of burning, body burn by location (body parts generally exposed in social environment or parts culturally perceived as sensitive areas of body), and intent of injury had significant correlation with irrational beliefs. The models predicted 15.5% (P < .001) of irrational beliefs. Considering to irrational beliefs and development of facilities for screening is necessary. Moreover, consultation with mental health experts after burn injuries is highly recommended.
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| 8. |
- Zare, Zahra, et al.
(författare)
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Irrational thinking and its predictors among burn patients
- 2018
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Ingår i: Injury Prevention. - : BMJ Publishing Group Ltd. - 1475-5785 .- 1353-8047. ; 24
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Konferensbidrag (refereegranskat)abstract
- Background Burn injuries are most certainly stressful events, particularly when permanent disfigurement is a result. This situation can lead to the onset of irrational beliefs which can in turn lead to long-term psychological problems such as depression, anxiety, shame, guilt, posttraumatic stress, etc. The objective of this study is to determinate predictors of irrational beliefs among burn patients in Iran. Method This cross-sectional study was carried out on a total of 329 burn patients. In order to assess irrational beliefs, Scale for Irrational Thoughts after Burning (SITB) was used. To identify predictors of irrational thoughts, both bivariate and multivariate analysis method were conducted. In multivariate linear regression, forward strategy was used for building the model. Preliminary variable selection for model design was based on a p<0.2 and final decision for keeping the variables in the model was based on a p<0.05. Results The results of bivariate analysis showed that body burned location (body parts generally exposed in social environment or parts culturally perceived as sensitive areas of body), marital status, urbanities, age group, geographical areas, etiology of burning and intent of injury had significant relationships with irrational thoughts. (p<0.05) Using forward linear regression, gender, marital status, geographical areas, etiology of burning, body burned location (body parts generally exposed in social environment or parts culturally perceived as sensitive areas of body), and intent of injury were significant predictors of the SITB. The models predicted 15.5 percent (p<0.001) of irrational thoughts. Conclusion Considering to irrational thoughts and development of facilities for screening is necessary. Moreover, consultation with mental health experts after burn injuries is highly recommended.
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| 9. |
- Zare, Zahra, et al.
(författare)
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Psychometric Properties of a New Instrument for Assessing Irrational Thoughts in Burn Victims (Scale of Irrational Thoughts After Burn Injuries)
- 2017
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Ingår i: Journal of Burn Care & Research. - : Oxford University Press. - 1559-047X .- 1559-0488. ; 38:5, s. e834-e841
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to develop and evaluate a scale for assessing irrational thoughts among burned patients. The present study was mixed (qualitative-methodologic) which was performed in several stages such as investigating similar or related scales, interviewing with patients and psychologists. Content validity was calculated by modified KAPPA basis on relevance and clarity. The reliability of the scale was measured using internal consistency and the test-retest method. To determine the construct validity, exploratory factor analysis approach using maximum likelihood extraction with varimax rotation was conducted. A total of 329 burned patients were recruited from Tehran, Tabriz, and Kermanshah provinces of Iran. Modified kappa scores were 0.80 and 0.91 for relevance and clarity of the items included in scale. The Cronbach alpha for overall scale, subscale 1, and subscale 2 were 0.89, 0.88, and 0.8, respectively. Test-retest reliability was also acceptable (intraclass correlation coefficient = 0.80). The best solution from the maximum likelihood analysis of the 39 items of the scale revealed two factors corresponding to the two subscales with 14 items that subscale 1 (self-acceptance) consisted of 10 statements accounting for 60% of the variance (eigenvalue = 5.04) and subscale 2 (distastefulness and pity) consisted of four statements accounting for 40% of the variance (eigenvalue = 1.53). The scale reflects acceptable levels of validity and reliability in assessing the irrational thoughts among Iranian patients. Moreover, the testing populations of both patients with burned faces and patients with other burned body parts indicates that the scale may also be applicable for patients' burn disfigurements on any part of their bodies.
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| 10. |
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| 11. |
- Ahlqvist, Emma, et al.
(författare)
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High-resolution mapping of a complex disease, a model for rheumatoid arthritis, using heterogeneous stock mice
- 2011
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Ingår i: Human Molecular Genetics. - Oxford : Oxford University Press. - 0964-6906 .- 1460-2083. ; 20:15, s. 3031-3041
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Tidskriftsartikel (refereegranskat)abstract
- Resolving the genetic basis of complex diseases like rheumatoid arthritis will require knowledge of the corresponding diseases in experimental animals to enable translational functional studies. Mapping of quantitative trait loci in mouse models of arthritis, such as collagen-induced arthritis (CIA), using F(2) crosses has been successful, but can resolve loci only to large chromosomal regions. Using an inbred-outbred cross design, we identified and fine-mapped CIA loci on a genome-wide scale. Heterogeneous stock mice were first intercrossed with an inbred strain, B10.Q, to introduce an arthritis permitting MHCII haplotype. Homozygous H2(q) mice were then selected to set up an F(3) generation with fixed major histocompatibility complex that was used for arthritis experiments. We identified 26 loci, 18 of which are novel, controlling arthritis traits such as incidence of disease, severity and time of onset and fine-mapped a number of previously mapped loci. © The Author 2011. Published by Oxford University Press. All rights reserved.
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| 12. |
- Andersson, Agneta, et al.
(författare)
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Alcohol use among university students in Sweden measured by an electronic screening instrument
- 2009
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 9:229
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Tidskriftsartikel (refereegranskat)abstract
- Background: Electronic-based alcohol screening and brief interventions for university students with problem drinking behaviours forms an important means by which to identify risky drinkers. Methods: In this study an e-SBI project was implemented to assess drinking patterns, and to provide personalised feedback about alcohol consumption and related health problems, to students in a Swedish university. In this study, third semester university students (n = 2858) from all faculties (colleges) at the University were invited to participate in e-SBI screenings. This study employed a randomised controlled trial, with respondents having a equal chance of being assigned to a limited, or full-feedback response. Results: The study shows that high risk drinkers tend to underestimate their own consumption compared to others, and that these high risk drinkers experience more negative consequences after alcohol intake, than other respondents. There was a strong belief, for both high-and low-risk drinkers, that alcohol helped celebrations be more festive. This study also confirms findings from other study locations that while males drank more than females in our study population; females reached the same peak alcohol blood concentrations as males. Conclusion: Obtaining clear and current information on drinking patterns demonstrated by university students can help public health officials, university administration, and local health care providers develop appropriate prevention and treatment strategies.
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| 13. |
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| 14. |
- Bendtsen, Preben, et al.
(författare)
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Referral to an electronic screening and brief alcohol intervention in primary health care in Sweden : Impact of staff referral to the computer
- 2011
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Ingår i: International Journal of Telemedicine and Applications. - : Hindawi Limited. - 1687-6415 .- 1687-6423. ; 918763
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper was to evaluate whether primary health care staff's referral of patients to perform an electronic screening and brief intervention (e-SBI) for alcohol use had a greater impact on change in alcohol consumption after 3 month, compared to patients who performed the test on their own initiative. Staff-referred responders reported reduced weekly alcohol consumption with an average decrease of 8.4 grams. In contrast, self-referred responders reported an average increase in weekly alcohol consumption of 2.4 grams. Staff-referred responders reported a 49 reduction of average number of heavy episodic drinking (HED) occasions per month. The corresponding reduction for self-referred responders was 62. The differences between staff- and self-referred patient groups in the number who moved from risky drinking to nonrisky drinking at the followup were not statistically significant. Our results indicate that standalone computers with touchscreens that provide e-SBIs for risky drinking have the same effect on drinking behaviour in both staff-referred patients and self-referred patients. Copyright © 2011 Preben Bendtsen et al.
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| 15. |
- Bhattachariya, Anirban, et al.
(författare)
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Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 215:3, s. 133-143
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Tidskriftsartikel (refereegranskat)abstract
- Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein.
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| 16. |
- Björklund, Åsa K., et al.
(författare)
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Domain Rearrangements in Protein Evolution
- 2005
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 353:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Most eukaryotic proteins are multi-domain proteins that are created from fusions of genes, deletions and internal repetitions. An investigation of such evolutionary events requires a method to find the domain architecture from which each protein originates. Therefore, we defined a novel measure, domain distance, which is calculated as the number of domains that differ between two domain architectures. Using this measure the evolutionary events that distinguish a protein from its closest ancestor have been studied and it was found that indels are more common than internal repetition and that the exchange of a domain is rare. Indels and repetitions are common at both the N and C-terminals while they are rare between domains. The evolution of the majority of multi-domain proteins can be explained by the stepwise insertions of single domains, with the exception of repeats that sometimes are duplicated several domains in tandem. We show that domain distances agree with sequence similarity and semantic similarity based on gene ontology annotations. In addition, we demonstrate the use of the domain distance measure to build evolutionary trees. Finally, the evolution of multi-domain proteins is exemplified by a closer study of the evolution of two protein families, non-receptor tyrosine kinases and RhoGEFs.
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| 17. |
- Björklund, Åsa K., et al.
(författare)
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Expansion of Protein Domain Repeats
- 2006
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Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 2:8, s. 959-970
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Tidskriftsartikel (refereegranskat)abstract
- Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e. g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.
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| 18. |
- Dahan, Diana, et al.
(författare)
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Induction of angiotensin converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.
- 2014
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Ingår i: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 307:12, s. 1093-1101
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin converting enzyme in the aorta but not in the bladder where angiotensin converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target.
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| 19. |
- Dahan, Diana, et al.
(författare)
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MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
- 2017
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:4, s. 246-256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.
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| 20. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 21. |
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| 22. |
- Ekman, Diana, 1977-
(författare)
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Domain rearrangement and creation in protein evolution
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins are composed of domains, recurrent protein fragments with distinct structure, function and evolutionary history. Some domains exist only as single domain proteins, however, a majority of them are also combined with other domains. Domain rearrangements are important in the evolution of new proteins as new functionalities can arise in a single evolutionary event. In addition, the domain repertoire can be expanded through mutations of existing domains and de novo creation. The processes of domain rearrangement and creation have been the focus of this thesis.According to our estimates about 65% of the eukaryotic and 40% of the prokaryotic proteins are of multidomain type. We found that insertion of a single domain at the N- or C-terminus was the most common event in the creation of novel multidomain architectures. However, domain repeats deviate from this pattern and are often expanded through duplications of several domains. Next, by mapping domain combinations onto an evolutionary tree we estimated that roughly one domain architecture has been created per million years, with the highest rates in metazoa. Much of this so called explosion of new architectures in metazoa seems to be explained by a set of domains amenable to exon shuffling. In contrast to domain architectures, most known domain families evolved early. However, many proteins have incomplete domain coverage, and could hence contain de novo created domains. In Saccharomyces cerevisiae, however, species specific sequences constitute only a minor fraction of the proteome, and are often short, disordered sequences located at the protein termini.
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| 23. |
- Ekman, Diana, et al.
(författare)
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Identifying and Quantifying Orphan Protein Sequences in Fungi
- 2010
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 396:2, s. 396-405
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Tidskriftsartikel (refereegranskat)abstract
- For large regions of many proteins, and even entire proteins, no homology to known domains or proteins can be detected. These sequences are often referred to as orphans. Surprisingly, it has been reported that the large number of orphans is sustained in spite of a rapid increase of available genomic sequences. However, it is believed that de novo creation of coding sequences is rare in comparison to mechanisms such as domain shuffling and gene duplication; hence, most sequences should have homologs in other genomes. To investigate this, the sequences of 19 complete fungi genomes were compared. By using the phylogenetic relationship between these genomes, we could identify potentially de novo created orphans in Saccharomyces cerevisiae. We found that only a small fraction, <2%, of the S. cerevisiae proteome is orphan, which confirms that de novo creation of coding sequences is indeed rare. Furthermore, we found it necessary to compare the most closely related species to distinguish between de novo created sequences and rapidly evolving sequences where homologs are present but cannot be detected. Next, the orphan proteins (OPs) and orphan domains (ODs) were characterized. First, it was observed that both OPs and ODs are short. In addition, at least some of the OPs have been shown to be functional in experimental assays, showing that they are not pseudogenes. Furthermore, in contrast to what has been reported before and what is seen for older orphans, S. cerevisiae specific ODs and proteins are not more disordered than other proteins. This might indicate that many of the older, and earlier classified, orphans indeed are fast-evolving sequences. Finally, >90% of the detected ODs are located at the protein termini, which suggests that these orphans could have been created by mutations that have affected the start or stop codons.
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| 24. |
- Ekman, Diana, et al.
(författare)
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Multi-domain Proteins in the Three Kingdoms of Life : Orphan Domains and Other Unassigned Regions
- 2005
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 348:1, s. 241-243
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of the proteomes from different organisms have provided valuable information about protein domain distribution in the kingdoms of life. Earlier studies have been limited by the fact that only about 50% of the proteomes could be matched to a domain. Here, we have extended these studies by including less well-defined domain definitions, Pfam-B and clustered domains, MAS, in addition to Pfam-A and SCOP domains. It was found that a significant fraction of these domain families are homologous to Pfam-A or SCOP domains. Further, we show that all regions that do not match a Pfam-A or SCOP domain contain a significantly higher fraction of disordered structure. These unstructured regions may be contained within orphan domains or function as linkers between structured domains. Using several different definitions we have re-estimated the number of multi-domain proteins in different organisms and found that several methods all predict that eukaryotes have approximately 65% multi-domain proteins, while the prokaryotes consist of approximately 40% multi-domain proteins. However, these numbers are strongly dependent on the exact choice of cut-off for domains in unassigned regions. In conclusion, all eukaryotes have similar fractions of multidomain proteins and disorder, whereas a high fraction of repeating domain is distinguished only in multicellular eukaryotes. This implies a role for repeats in cell-cell contacts while the other two features are important for intracellular functions.
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| 25. |
- Ekman, Diana, et al.
(författare)
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Quantification of the Elevated Rate of Domain Rearrangements in Metazoa
- 2007
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 372:5, s. 1337-1348
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Tidskriftsartikel (refereegranskat)abstract
- Most eukaryotic proteins consist of multiple domains created through gene fusions or internal duplications. The most frequent change of a domain architecture (DA) is insertion or deletion of a domain at the N or C terminus. Still, the mechanisms underlying the evolution of multidomain proteins are not very well studied. Here, we have studied the evolution of multidomain architectures (MDA), guided by evolutionary information in the form of a phylogenetic tree. Our results show that Pfam domain families and MDAs have been created with comparable rates (0.1–1 per million years (My)). The major changes in DA evolution have occurred in the process of multicellularization and within the metazoan lineage. In contrast, creation of domains seems to have been frequent already in the early evolution. Furthermore, most of the architectures have been created from older domains or architectures, whereas novel domains are mainly found in single-domain proteins. However, a particular group of exon-bordering domains may have contributed to the rapid evolution of novel multidomain proteins in metazoan organisms. Finally, MDAs have evolved predominantly through insertions of domains, whereas domain deletions are less common. In conclusion, the rate of creation of multidomain proteins has accelerated in the metazoan lineage, which may partly be explained by the frequent insertion of exon-bordering domains into new architectures. However, our results indicate that other factors have contributed as well.
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| 26. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
-
Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 27. |
- Ekman, Mari, et al.
(författare)
-
Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness. c-Myc, NF-κB and SMAD3, all of which repress miR-29, were activated in the rat detrusor following partial bladder outlet obstruction but at different times. c-Myc and NF-κB activation occurred early after obstruction, and SMAD3 phosphorylation increased later, with a significant elevation at 6 weeks. c-Myc, NF-κB and SMAD3 activation, respectively, correlated with repression of miR-29b and miR-29c at 10 days of obstruction and with repression of miR-29c at 6 weeks. An mRNA microarray analysis showed that the reduction of miR-29 following outlet obstruction was associated with increased levels of miR-29 target mRNAs, including mRNAs for tropoelastin, the matricellular protein Sparc and collagen IV. Outlet obstruction increased protein levels of eight out of eight examined miR-29 targets, including tropoelastin and Sparc. Transfection of human bladder smooth muscle cells with antimiR-29c and miR-29c mimic caused reciprocal changes in target protein levels in vitro. Tamoxifen inducible and smooth muscle-specific deletion of Dicer in mice reduced miR-29 expression and increased tropoelastin and the thickness of the basal lamina surrounding smooth muscle cells in the bladder. It also increased detrusor stiffness independent of outlet obstruction. Taken together, our study supports a model where the combined repressive influences of c-Myc, NF-κB and SMAD3 reduce miR-29 in bladder outlet obstruction, and where the resulting drop in miR-29 contributes to matrix remodeling and altered passive mechanical properties of the detrusor.
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| 28. |
- Hien Tran, Thi, et al.
(författare)
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Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.
- 2016
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 291:7, s. 68-3552
-
Tidskriftsartikel (refereegranskat)abstract
- Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hyper-contractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, qPCR and western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers was increased in isolated smooth muscle cells cultured under high compared to low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization and myocardin related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.
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| 29. |
- Howell, Marcia, et al.
(författare)
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Switched On : How the Timing of Aversive Content in Traffic Safety Videos Impact Psychophysiological Indicators of Message Processing
- 2019
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Ingår i: Health Communication. - : Taylor & Francis. - 1041-0236 .- 1532-7027. ; 34:13, s. 1663-1672
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates how timing of the introduction of unpleasant emotional tone in a traffic safety video impacts the intensity of the viewer?s emotional experience. Traffic safety advertising is a multi-million-dollar business in the United States. In many instances, 30?60?s ads are produced to raise awareness of the consequences of unsafe behaviors with the expectation that simply providing information will motivate safer behaviors. Producing videos intended to generate behavior change requires a complex understanding of what motivates behavior. Behavior change theory, neuroscience, and psychophysiology all provide guidance to improve the persuasive power of traffic safety videos. This study consisted of a 3 (message tone)???3 (video)???4 (order) repeated measures within subjects designed experiment. Participants (N?=?75) were 20?30-year-old men who were shown nine traffic safety videos. Arousal intensity, attention, and negative emotion were tracked with the psychophysiological measures of skin conductance (measuring intensity of arousal), heart rate (measuring attention paid during the video), and corrugator muscle activation (measuring the negative emotional experience). Videos with three different aversive tones were used, low, high, and videos in which the tone switched from low to high aversive. Aversive tone is defined as stimuli that motivate a desire to escape or avoid something like death or pain. All videos were designed to prevent motor vehicle crashes. The results obtained from this study indicate that when attempting to persuade males aged 20?30 to practice safer driving behaviors, switched message tone appears to be the most effective message design in terms the intensity of emotional arousal and maintenance of attention.
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| 30. |
- Hudson, Diana, et al.
(författare)
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Factors associated with injuries occurring aboard vessels in Alaska : differences between residents and nonresidents.
- 2006
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Ingår i: Journal of Travel Medicine. - : Oxford University Press (OUP). - 1195-1982 .- 1708-8305. ; 13:2, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over the past decade, visitors to Alaska have spent increasing amounts of time engaged in water-based recreational activities aboard vessels of various sizes. Serious vessel-related injuries to travelers in Alaska involve not only medical care from unfamiliar health care providers and facilities but also entail the loss of vacation time and the need for injured travelers to return to their homes under less than optimal traveling conditions. METHODS: This study employed a retrospective, case-comparison analysis to identify differences in factors associated with recreational injuries acquired aboard watercraft that resulted in hospitalizations of residents and nonresidents of Alaska during 1991 to 2000. Tests of proportions were conducted to elucidate differences in demographic characteristics and injury precursors between the two subgroups. Specific injury outcomes were then tested for significance using odds ratios. RESULTS: Alaska residents and nonresidents demonstrated significant differences for both demographic factors and factors describing events leading to injuries, and for injury outcomes. Nonresidents were more likely to be 65 years or older, female, and aboard cruise ships when injuries occurred. Nonresidents were more likely to suffer fracture injuries, to suffer injuries with Abbreviated Injury Scores greater than 2, to experience posthospital discharges to sites other than their homes, and to experience postinjury disabilities. CONCLUSIONS: Alaska residents and nonresidents in this study showed significant differences in demographics, precipitating events, and injury outcomes. The findings lend support for targeted safety promotion programs.
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| 31. |
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| 32. |
- Johansson, Anna, 1975-
(författare)
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Societal risk and safety management : Policy diffusion, management structures and perspectives at the municipal level in Sweden
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This compilation thesis investigates risk and safety management at the Swedish local governmentallevel. It sets special focus on municipal implementation of overall international and nationalstrategies and objectives regarding holistic, cross-sectorial and multi-strategic risk and safetywork, and the prevention of accidents and injuries.The overall aim for this thesis have been to empirically map and provide an overview of theadministrative structures for, and the prevailing management perspectives applied in the societalrisk and safety management in Sweden, as well as to study the diffusion of strategic intentions forthis area down to the municipal level.Three different sources constitute the thesis empirical base: two different set of official planningdocuments, written by Swedish municipal officials on commission of the local politiciansand one set of data from a survey investigation with municipal officials representing differentdepartments/functions. The documents were investigated using content analysis, while datafrom the survey were analyzed using statistical measures.This thesis provides through its empirical works an outlook on the general characteristics andarchetypical features of the Swedish local level’s administrative structures and managementperspective on risk and safety management; and proposes a municipal typology and a set of valuecharacters for allocation and institutionalization of risk and safety-tasks. This thesis also suggestsa conceptual framework for overviewing risk and safety management’s systemic steering elementsin its framework report. Based on the findings made, it seems as if the local level’s compliance tothe strategic level’s ambitions for the risk and safety area is hindered by practical implementationdifficulties and that much work remains in order to reach stated strategic objectives regardingholistic, inter-sectorial and multi-strategic management approaches, and preventive risk andsafety work.
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| 33. |
- Karbalaei, Mardjaneh, et al.
(författare)
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Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of miR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the miR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced miR-132/212 in human detrusor cells. To identify miR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between miR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases miR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.
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| 34. |
- Kazemi, Ali, et al.
(författare)
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Differing attitudes toward health and sickness
- 2014
-
Ingår i: Encyclopedia of human services and diversity. - 2455 Teller Road, Thousand Oaks California 91320 United States : Sage Publications. - 9781452287485 - 9781483346663 ; , s. 616-618
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Bokkapitel (refereegranskat)
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| 35. |
- Khoso, Ajmal Khan, et al.
(författare)
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Comparison of Highway Crash Reporting in Pakistan With the World Health Organization Injury Surveillance Guidelines
- 2011
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Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 12:3, s. 279-282
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the crash reporting system of National Highways Motorways Police (NHMP), Pakistan, with the World Health Organization (WHO) injury surveillance guidelines. Methods: Based on information collected from field observations, key informant interviews, and review of official documents, this note firstly describes the reporting system according to the components of a surveillance system. Then the reporting is compared with WHO criteria for designing and building an injury surveillance system and attributes of such a system. Results: After a crash, a patrol officer communicates the information to the higher police authorities by wireless, fax, and on paper in the first 24 hours. Microcomputer Accident Analysis Package (MAAP) Performa filed by the officers are collected at a central location in the following 4 days, and reports are published biannually. Notable deficiencies in the reporting were nonidentification of stakeholders for data utilization and limited prospects of data recording process modification and its monitoring. Moreover, crash and injury definitions do not conform to international standards practiced elsewhere. Conclusion: NHMP crash reporting needs to be simplified and standardized, and steps should be taken to improve its utilization for prevention purposes.
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| 36. |
- Kierczak, Marcin, 1981-, et al.
(författare)
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Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
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| 37. |
- Kylberg, Elisabeth, et al.
(författare)
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Nutritional services and assessment
- 2014
-
Ingår i: Encyclopedia of Human Services and Diversity. - Thousand Oaks, California : Sage Publications. - 9781452287485 - 9781483346663 ; , s. 975-977
-
Bokkapitel (refereegranskat)
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| 38. |
- Leijon, Matti, et al.
(författare)
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Improvement of physical activity by a kiosk-based electronic screening and brief intervention in routine primary health care : Patient-initiated versus staff-referred
- 2011
-
Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 13:4, s. e99-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interactive behavior change technology (eg, computer programs, Internet websites, and mobile phones) may facilitate the implementation of lifestyle behavior interventions in routine primary health care. Effective, fully automated solutions not involving primary health care staff may offer low-cost support for behavior change. Objectives: We explored the effectiveness of an electronic screening and brief intervention (e-SBI) deployed through a stand-alone information kiosk for promoting physical activity among sedentary patients in routine primary health care. We further tested whether its effectiveness differed between patients performing the e-SBI on their own initiative and those referred to it by primary health care staff. Methods: The e-SBI screens for the physical activity level, motivation to change, attitudes toward performing the test, and physical characteristics and provides tailored feedback supporting behavior change. A total of 7863 patients performed the e-SBI from 2007 through 2009 in routine primary health care in Östergötland County, Sweden. Of these, 2509 were considered not sufficiently physically active, and 311 of these 2509 patients agreed to participate in an optional 3-month follow-up. These 311 patients were included in the analysis and were further divided into two groups based on whether the e-SBI was performed on the patient's own initiative (informed by posters in the waiting room) or if the patient was referred to it by staff. A physical activity score representing the number of days being physically active was compared between baseline e-SBI and the 3-month follow-up. Based on physical activity recommendations, a score of 5 was considered the cutoff for being sufficiently physically active. Results: In all, 137 of 311 patients (44%) were sufficiently physically active at the 3-month follow-up. The proportion becoming sufficiently physically active was 16/55 (29%), 40/101 (40%), and 81/155 (52%) for patients with a physical activity score at baseline of 0, 1 to 2, and 3 to 4, respectively. The patient-initiated group and staff-referred group had similar mean physical activity scores at baseline (2.1, 95% confidence interval [CI] 1.8-2.3, versus 2.3, 95% CI 2.1-2.5) and at follow-up, (4.1, 95% CI 3.4-4.7, vs 4.2, 95% CI 3.7-4.8). Conclusions: Among the sedentary patients in primary health care who participated in the follow-up, the e-SBI appeared effective at promoting short-term improvement of physical activity for about half of them. The results were similar when the e-SBI was patient-initiated or staff-referred. The e-SBI may be a low-cost complement to lifestyle behavior interventions in routine primary health care and could work as a stand-alone technique not requiring the involvment of primary health care staff. © Matti Leijon, Daniel Arvidsson, Per Nilsen, Diana Stark Ekman, Siw Carlfjord, Agneta Andersson, Anne Lie Johansson, Preben Bendtsen.
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| 39. |
- Leijon, Matti, 1970-, et al.
(författare)
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Is there a demand for physical activity interventions from health care providers? : Findings from a population survey
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10:34
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Health care providers in many countries have delivered interventions to improve physical activity levels among their patients. Thus far, less is known about the population's interest to increase their physical activity levels and their opinion about the health care provider's role in physical activity promotion. The aims of this paper were to investigate the self-reported physical activity levels of the population and intention to increase physical activity levels, self-perceived need for support, and opinions about the responsibilities of both individuals and health care providers to promote physical activity.Methods: A regional public health survey was mailed to 13 440 adults (aged 18-84 years) living in Östergötland County (Sweden) in 2006. The survey was part of the regular effort by the regional Health Authorities.Results: About 25% of the population was categorised as physically active, 38% as moderately active, 27% as somewhat active, and 11% as low active. More than one-third (37%) had no intentions to increase their physical activity levels, 36% had thought about change, while 27% were determined to change. Lower intention to change was mainly associated with increased age and lower education levels. 28% answered that physical activity was the most important health-related behaviour to change "right now" and 15% of those answered that they wanted or needed support to make this change. Of respondents who might be assumed to be in greatest need of increased activity (i.e. respondents reporting poor general health, BMI>30, and inactivity) more than one-quarter wanted support to make improvements to their health. About half of the respondents who wanted support to increase their physical activity levels listed health care providers as a primary source for support.Conclusion: These findings suggest that there is considerable need for physical activity interventions in this population. Adults feel great responsibility for their own physical activity levels, but also attribute responsibility for promoting increased physical activity to health care practitioners.
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| 40. |
- Leijon, Matti, et al.
(författare)
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Is there a demand for physical activity interventions provided by the health care sector? Findings from a population survey
- 2010
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Health care providers in many countries have delivered interventions to improve physical activity levels among their patients. Thus far, less is known about the population's interest to increase their physical activity levels and their opinion about the health care provider's role in physical activity promotion. The aims of this paper were to investigate the self-reported physical activity levels of the population and intention to increase physical activity levels, self-perceived need for support, and opinions about the responsibilities of both individuals and health care providers to promote physical activity. Methods: A regional public health survey was mailed to 13 440 adults (aged 18-84 years) living in Ostergotland County (Sweden) in 2006. The survey was part of the regular effort by the regional Health Authorities. Results: About 25% of the population was categorised as physically active, 38% as moderately active, 27% as somewhat active, and 11% as low active. More than one-third (37%) had no intentions to increase their physical activity levels, 36% had thought about change, while 27% were determined to change. Lower intention to change was mainly associated with increased age and lower education levels. 28% answered that physical activity was the most important health-related behaviour to change "right now" and 15% of those answered that they wanted or needed support to make this change. Of respondents who might be assumed to be in greatest need of increased activity (i.e. respondents reporting poor general health, BMI>30, and inactivity) more than one-quarter wanted support to make improvements to their health. About half of the respondents who wanted support to increase their physical activity levels listed health care providers as a primary source for support. Conclusions: These findings suggest that there is considerable need for physical activity interventions in this population. Adults feel great responsibility for their own physical activity levels, but also attribute responsibility for promoting increased physical activity to health care practitioners.
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| 41. |
- Light, Sara, et al.
(författare)
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Long indels are disordered : A study of disorder and indels in homologous eukaryotic proteins
- 2013
-
Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1834:5, s. 890-897
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Tidskriftsartikel (refereegranskat)abstract
- Proteins evolve through point mutations as well as by insertions and deletions (indels). During the last decade it has become apparent that protein regions that do not fold into three-dimensional structures, i.e. intrinsically disordered regions, are quite common. Here, we have studied the relationship between protein disorder and indels using HMM-HMM pairwise alignments in two sets of orthologous eukaryotic protein pairs. First, we show that disordered residues are much more frequent among indel residues than among aligned residues and, also are more prevalent among indels than in coils. Second, we observed that disordered residues are particularly common in longer indels. Disordered indels of short-to-medium size are prevalent in the non-terminal regions of proteins while the longest indels, ordered and disordered alike, occur toward the termini of the proteins where new structural units are comparatively well tolerated. Finally, while disordered regions often evolve faster than ordered regions and disorder is common in indels, there are some previously recognized protein families where the disordered region is more conserved than the ordered region. We find that these rare proteins are often involved in information processes, such as RNA processing and translation. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.
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| 42. |
- Light, Sara, et al.
(författare)
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Protein Expansion Is Primarily due to Indels in Intrinsically Disordered Regions
- 2013
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 30:12, s. 2645-2653
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Tidskriftsartikel (refereegranskat)abstract
- Proteins evolve not only through point mutations but also by insertion and deletion events, which affect the length of the protein. It is well known that such indel events most frequently occur in surface-exposed loops. However, detailed analysis of indel events in distantly related and fast-evolving proteins is hampered by the difficulty involved in correctly aligning such sequences. Here, we circumvent this problem by first only analyzing homologous proteins based on length variation rather than pairwise alignments. Using this approach, we find a surprisingly strong relationship between difference in length and difference in the number of intrinsically disordered residues, where up to three quarters of the length variation can be explained by changes in the number of intrinsically disordered residues. Further, we find that disorder is common in both insertions and deletions. A more detailed analysis reveals that indel events do not induce disorder but rather that already disordered regions accrue indels, suggesting that there is a lowered selective pressure for indels to occur within intrinsically disordered regions.
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| 43. |
- Lindqvist, C. Mårten, et al.
(författare)
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Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
-
Tidskriftsartikel (refereegranskat)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Lindqvist, C Mårten, et al.
(författare)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 48. |
- Martínez Barrio, Álvaro, et al.
(författare)
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The genetic basis for ecological adaptation of the Atlantic herring revealed by genome sequencing
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Ecological adaptation is of major relevance to speciation and sustainable population management, but the underlying genetic factors are typically hard to study in natural populations due to genetic differentiation caused by natural selection being confounded with genetic drift in subdivided populations. Here, we use whole genome population sequencing of Atlantic and Baltic herring to reveal the underlying genetic architecture at an unprecedented detailed resolution for both adaptation to a new niche environment and timing of reproduction. We identify almost 500 independent loci associated with a recent niche expansion from marine (Atlantic Ocean) to brackish waters (Baltic Sea), and more than 100 independent loci showing genetic differentiation between spring- and autumn-spawning populations irrespective of geographic origin. Our results show that both coding and non-coding changes contribute to adaptation. Haplotype blocks, often spanning multiple genes and maintained by selection, are associated with genetic differentiation.
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- Needhamsen, Maria, et al.
(författare)
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Integration of small RNAs from plasma and cerebrospinal fluid for classification of multiple sclerosis
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Multiple Sclerosis (MS) is an autoimmune, neurological disease, commonly presenting with a relapsing-remitting form, that later converts to a secondary progressive stage, referred to as RRMS and SPMS, respectively. Early treatment slows disease progression, hence, accurate and early diagnosis is crucial. Recent advances in large-scale data processing and analysis have progressed molecular biomarker development. Here, we focus on small RNA data derived from cell-free cerebrospinal fluid (CSF), cerebrospinal fluid cells, plasma and peripheral blood mononuclear cells as well as CSF cell methylome data, from people with RRMS (n = 20), clinically/radiologically isolated syndrome (CIS/RIS, n = 2) and neurological disease controls (n = 14). We applied multiple co-inertia analysis (MCIA), an unsupervised and thereby unbiased, multivariate method for simultaneous data integration and found that the top latent variable classifies RRMS status with an Area Under the Receiver Operating Characteristics (AUROC) score of 0.82. Variable selection based on Lasso regression reduced features to 44, derived from the small RNAs from plasma (20), CSF cells (8) and cell-free CSF (16), with a marginal reduction in AUROC to 0.79. Samples from SPMS patients (n = 6) were subsequently projected on the latent space and differed significantly from RRMS and controls. On contrary, we found no differences between relapse and remission or between inflammatory and non-inflammatory disease controls, suggesting that the latent variable is not prone to inflammatory signals alone, but could be MS-specific. Hence, we here showcase that integration of small RNAs from plasma and CSF can be utilized to distinguish RRMS from SPMS and neurological disease controls.
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