| 1. |
- Olsson, Andreas, et al.
(author)
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The Orthostatic Hypotension Questionnaire in Swedish tested in patients with parkinsonism
- 2020
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In: Brain and Behavior. - : Wiley. - 2162-3279. ; 10:9
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Journal article (peer-reviewed)abstract
- Background: Orthostatic hypotension (OH) is common among older people and in particular in conditions like Parkinson’s disease (PD). The OH Questionnaire (OHQ) has been proposed as a useful patient-reported assessment tool consisting of the OH Symptom Assessment (OHSA), OH Daily Activity Scale (OHDAS), and a composite score. Aims of the Study: To translate the OHQ into Swedish and assess its psychometric properties. Methods: Following forward–backward translation, the Swedish OHQ was field-tested (n = 6) for relevance, comprehensibility, and respondent burden. It was then tested regarding scaling assumptions, targeting, reliability, and construct validity in persons with PD (n = 27) and multiple system atrophy (n = 2). Results: The Swedish OHQ was considered relevant and easy to use, with a mean completion time of 5.3 min. Scaling assumptions were acceptable for OHSA and OHDAS (corrected item-total correlations,.30–.67) but not for the total score (.12–.69). Floor/ceiling effects were ≤3.4% and reliability was >.64. Construct validity was supported by expected correlations with the SCOPA-AUT, RAND-36, and blood pressure measurements. Conclusions: The Swedish OHQ was well received, and psychometric results suggest that the OHQ (particularly the OHDAS) is a useful tool for OH assessment in parkinsonian disorders. Further testing in larger samples is needed.
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| 2. |
- Adermark, Louise, 1974, et al.
(author)
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Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens.
- 2011
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In: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 16:1, s. 43-54
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Journal article (peer-reviewed)abstract
- ABSTRACT Elevated dopamine levels are believed to contribute to the rewarding sensation of ethanol (EtOH), and previous research has shown that strychnine-sensitive glycine receptors in the nucleus accumbens (nAc) are involved in regulating dopamine release and in mediating the reinforcing effects of EtOH. Furthermore, the osmoregulator taurine, which is released from astrocytes treated with EtOH, can act as an endogenous ligand for the glycine receptor, and increase extracellular dopamine levels. The aim of this study was to address if EtOH-induced swelling of astrocytes could contribute to elevated dopamine levels by increasing the extracellular concentration of taurine. Cell swelling was estimated by optical sectioning of fluorescently labeled astrocytes in primary cultures from rat, and showed that EtOH (25-150 mM) increased astrocyte cell volumes in a concentration- and ion-dependent manner. The EtOH-induced cell swelling was inhibited in cultures treated with the Na(+)/K(+)/2Cl(-) cotransporter blocker furosemide (1 mM), Na(+)/K(+)-ATPase inhibitor ouabain (0.1 mM), potassium channel inhibitor BaCl(2) (50 microM) and in cultures containing low extracellular sodium concentration (3 mM). In vivo microdialysis performed in the nAc of awake and freely moving rats showed that local treatment with EtOH enhanced the concentrations of dopamine and taurine in the microdialysate, while glycine and beta-alanine levels were not significantly modulated. EtOH-induced dopamine release was antagonized by local treatment with the glycine receptor antagonist strychnine (20 microM) or furosemide (100 microM or 1 mM). Furosemide also prevented EtOH-induced taurine release in the nAc. In conclusion, our data suggest that extracellular concentrations of dopamine and taurine are interconnected and that swelling of astrocytes contributes to the acute rewarding sensation of EtOH.
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| 3. |
- Ahearn, Thomas U., et al.
(author)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Journal article (peer-reviewed)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 4. |
- Alaie, Iman, et al.
(author)
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Uppsala Longitudinal Adolescent Depression Study (ULADS)
- 2019
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:3
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Journal article (peer-reviewed)abstract
- Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses.Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000).Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships.Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.
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| 5. |
- Björkholm, Anna-Mia, et al.
(author)
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BRC Globala standarden för livsmedelssäkerhet
- 2011
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Reports (other academic/artistic)abstract
- BRC är en förkortning för British Retail Consortium, som är en branschorganisation för de största detaljhandelskedjorna i Storbritannien. BRC står bakom BRC Global Standard for Food Safety, den globala standarden för livsmedelssäkerhet. Man kan se standarden som en checklista över vad som är viktigt i en livsmedelsindustri. Standarden ger svar på vad man behöver tänka på, och vilka faktorer man måste styra korrekt för att kunna tillverka och leverera produkter som är säkra och uppfyller lagkrav. Det är även möjligt att certifiera sig mot standarden. EU:s livsmedelsförordning slår fast att alla som på något sätt hanterar livsmedel skall arbeta enligt produktsäkerhetssystemet HACCP. HACCP står för Hazard Analysis Critical Control Point (Faroanalys och kritiska styrpunkter) och syftar till att hitta kritiska ställen i produktionen, samt styra dessa på bästa sätt. Den globala standarden för livsmedelssäkerhet bygger på HACCP. Kraven i den globala standarden för livsmedelssäkerhet är uppdelade i sju avsnitt. Utöver dessa finns avsnitt som ger en bakgrund samt beskriver dess omfattning och uppbyggnad. Ledningssystem består av olika element – man måste inventera nuläget, ha visioner om målen, planera, genomföra och styra, följa upp och förbättra. Det är en ständigt pågående process som tar mycket tid och kraft att starta upp. Rapport är ett resultat av projektet ”Kvalitets- och livsmedelssäkerhet för att möta marknadens krav/utbildningsmoduler” som har utförts inom ramen för Tillväxt Trädgård.
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| 6. |
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| 7. |
- Björkholm, Anna-Mia, et al.
(author)
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IP SIGILL : standard för kvalitetssäkrad produktion av frukt och grönt
- 2011
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Reports (other academic/artistic)abstract
- Denna rapport beskriver IP SIGILL – den svenska standarden för kvalitetssäkrad produktion av frukt och grönt. IP SIGILL-standarder finns för flera produktionsområden och ägs och utvecklas av Sigill Kvalitetssystem AB som är ett dotterbolag till LRF. Man strävar efter att göra skillnad inom områdena miljöhänsyn, livsmedelssäkerhet och djuromsorg. Det är inom dessa områden standarden ställer krav. Standarderna inom IP SIGILL bygger på HACCP-principerna. Då det gäller certifiering av primärproduktion av frukt och grönt är det standarden ”IP SIGILL Frukt & grönt” som är aktuell. Standarden är öppen för alla, uppdateras vartannat år, kräver tredjepartscertifiering och finns med tillägg för klimatcertifiering. Sigill Kvalitetssystem AB tillhandahåller stödmaterial som är till stor hjälp i certifieringsarbetet. Önskar man de mervärden IP SIGILL innefattar samt även möjlighet till export är det aktuellt med certifiering enligt standarden ”IP SIGILL GAP Frukt och grönt inklusive tillägg Svenskt Sigill”. Rapporten är en del av projektet ”Kvalitets- och livsmedelssäkerhet för att möta marknadens krav/utbildningsmoduler” som har utförts inom ramen för Tillväxt Trädgård.
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| 8. |
- Björkholm, Anna-Mia, et al.
(author)
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Livsmedelssäkerhet, ledningssystem, kvalitetssäkring och certifiering
- 2011
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Reports (other academic/artistic)abstract
- Livsmedelssäkerhet är ett begrepp som får allt större betydelse ju fler livsmedelsskandaler som skakar världen. Begreppet är centralt för alla som arbetar med primärproduktion och förädling av livsmedel. Det är en självklarhet att livsmedel ska produceras och hanteras på ett sätt som innebär att de är ofarliga för oss människor att äta. Begreppet kvalitet är viktigt och innefattar även aspekter som inte syns på produkterna t ex miljöbelastning och spårbarhet. Dessa typer av kvaliteter kan garanteras genom olika typer av certifiering. Det finns flera mervärden som uppnås då man certifierar sin produktion. Certifiering sker mot en standard, ett fastställt kravdokument, som då det gäller livsmedelssäkerhet oftast bygger på HACCP, det produktsäkerhetssystem som är norm inom EU. Det är godkända/ackrediterade certifieringsbolag som utför revisionerna mot standarden. Denna rapport är ett resultat av projektet ”Kvalitets- och livsmedelssäkerhet för att möta marknadens krav/utbildningsmoduler” som har utförts inom ramen för Tillväxt Trädgård.
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| 9. |
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| 10. |
- Conradsson, Mia, et al.
(author)
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Berg Balance Scale : intrarater test-retest reliability among older people dependent in activities of daily living and living in residential care facilities
- 2007
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In: Physical Therapy. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 87:9, s. 1155-1163
-
Journal article (peer-reviewed)abstract
- The Berg Balance Scale (BBS) is frequently used to assess balance in older people, but knowledge is lacking about the absolute reliability of BBS scores. The aim of this study was to investigate the absolute and relative intrarater test-retest reliability of data obtained with the BBS when it is used among older people who are dependent in activities of daily living and living in residential care facilities. The participants were 45 older people (36 women and 9 men) who were living in 3 residential care facilities. Their mean age was 82.3 years (SD=6.6, range=68-96), and their mean score on the Mini Mental State Examination was 17.5 (SD=6.3, range=4-30). The BBS was assessed twice by the same assessor. The intrarater test-retest reliability assessments were made at approximately the same time of day and with 1 to 3 days in between assessments. Absolute reliability was calculated using an analysis of variance with a 95% confidence level, as suggested by Bland and Altman. Relative reliability was calculated using the intraclass correlation coefficient (ICC). The mean score was 30.1 points (SD=15.9, range=3-53) for the first BBS test and 30.6 points (SD=15.6, range=4-54) for the retest. The mean absolute difference between the 2 tests was 2.8 points (SD=2.7, range=0-11). The absolute reliability was calculated as being 7.7 points, and the ICC was calculated to .97. Despite a high ICC value, the absolute reliability showed that a change of 8 BBS points is required to reveal a genuine change in function among older people who are dependent in activities of daily living and living in residential care facilities. This knowledge is important in the clinical setting when evaluating an individual's change in balance function over time in this group of older people.
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| 11. |
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| 12. |
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| 13. |
- Conradsson, Mia, et al.
(author)
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The Berg Balance Scale : Intra-rater reliability in older people dependent in ADL and living in residential care facilities
- 2006
-
Conference paper (other academic/artistic)abstract
- Aim: The aim of this study was to investigate the absolute and the relative intra-rater reliability of the Berg Balance Scale (BBS) among older people who are dependent in activities of daily living (ADL) and living in residential care facilities.Methods: The participants were 45 older people, 36 females and 9 men, who were dependent in ADL and living in three residential care facilities. Their mean age ± SD was 82.3 ± 6.6 (range 68-96) and mean ± SD of Mini Mental State Examination score was 17.5 ± 6.3 (range 4-30). The BBS was assessed twice by the same assessor, at approximately the same time of day, and with 1-3 days in between. The absolute reliability for the difference in score between the two test occasions was calculated with the Bland and Altman analysis of variance with 95 % confidence level. The relative reliability was calculated with Intraclass Correlation Coefficient (ICC).Results: For the first test of the BBS, mean ± SD was 30.1 ± 15.9 (range 3-53) points and for the retest 30.6 ± 15.6 (range 4-54). The absolute difference between the two test occasions was in mean ± SD 2.8 ± 2.7 (range 0-11) points. The absolute intra-rater reliability was calculated to 7.7 points and the ICC value was 0.97. Conclusions: Despite a high ICC value, the result of the absolute reliability show that a change of 8 BBS points is required to reveal a genuine change of function among older people who are dependent in ADL and living in residential care facilities. This knowledge is important in the clinical setting when evaluating an individual's change in balance function over time.
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| 14. |
- Cook, Michael B, et al.
(author)
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Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium.
- 2015
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531
-
Journal article (peer-reviewed)abstract
- Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
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| 15. |
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| 16. |
- Davidsson, Josef, et al.
(author)
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Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: An array-based genotype-phenotype correlation and a comprehensive review of previously published cases.
- 2008
-
In: Epilepsy Research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; Jun 6, s. 69-79
-
Journal article (peer-reviewed)abstract
- PURPOSE: To characterize a deletion of chromosome 2q at the molecular level in a patient suffering from severe epilepsy resembling severe myoclonic epilepsy of infancy/Dravet's syndrome (SMEI/DS) and to correlate other cases harboring deletions in the same region to morphological and clinical data. METHODS: Array-based comparative genomic hybridization (array CGH) was performed on DNA from the patient. Forty-three previously published cases reporting deletions within region 2q21-q31 were collected and analyzed regarding their cytogenetic and clinical data. RESULTS: A del(2)(q24.3q31.1) was detected in the patient, spanning a 10.4-megabase (Mb) region between 165.18 and 175.58Mb, harboring 47 genes. FISH analysis was performed, confirming this deletion. Twenty-two of the 43 previously published cases were seizure-positive. The most common dysmorphic features were ear abnormalities, microcephaly, micrognathia and brachysyndactyly for all patients as well as for solely the seizure-positive and -negative ones. For the 22 seizure-positive cases chromosome subband 2q24.3 constituted the smallest commonly deleted region among the majority of the cases, where subbands 2q22.1 and 2q33.3 represented the most proximal and distal breakpoint, respectively. CONCLUSIONS: Based on the early age of presentation and the severity of the epilepsy reported for the majority of the seizure-positive cases it was concluded that SMEI/DS could be the epileptic encephalopathy associated with deletions within the 2q22.1-q33.3 region, due to haploinsuffiency of SCN1A and/or complete or partial deletion of other voltage-gated sodium channel genes caused by the aberration. Furthermore, our study supports that array CGH is a competent technique for screening SCN1A mutation-negative patients diagnosed with SMEI/DS-like epilepsies and dysmorphic features, generating rapid and high-resolution data of genomic imbalances present in the patients.
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| 17. |
- Ding, Yuan C, et al.
(author)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Journal article (peer-reviewed)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 18. |
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| 19. |
- Escala-Garcia, Maria, et al.
(author)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
-
Journal article (peer-reviewed)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 20. |
- Fazey, Ioan, et al.
(author)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 21. |
- Frankowiack, Marcel, et al.
(author)
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IgA deficiency in wolves from Canada and Scandinavia
- 2015
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In: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 50:1, s. 26-28
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Journal article (peer-reviewed)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in both humans and selected breeds of domestic dogs. In both species, IgAD is associated with recurrent infections and immune mediated diseases. Previous results imply that IgAD is also common in the wild ancestor of domestic dogs, the gray wolf. Here, we report that serum IgA concentrations are significantly different in Scandinavian and Canadian wolves (p =3.252e-15) with an increased prevalence for IgAD in Scandinavian wolves (60%), which is as high as those found in high-risk dog breeds.
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| 22. |
- Gavali, Hamid, et al.
(author)
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Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction : A Nationwide Multicentre Study
- 2021
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In: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 62:6, s. 918-926
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Journal article (peer-reviewed)abstract
- Objective: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study.Methods: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR.Results: Some 126 radically surgically treated AGI patients were identified – 102 graft infections and 24 endograft infections – treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p =.46), or long term five year survival (48.2% vs. 49.9%, p =.87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p =.56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 – 14.8), coronary artery disease (OR 4.2, CI 1.2 – 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 – 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 – 0.9).Conclusion: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.
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| 23. |
- Gavali, Hamid, et al.
(author)
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Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections
- 2023
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 66:3, s. 397-406
-
Journal article (peer-reviewed)abstract
- Objective: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort.Methods: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality.Results: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan -Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan -Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 -1.5).Conclusion: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.
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| 24. |
- Gavali, Hamid, et al.
(author)
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Semi-Conservative Treatment Versus Surgery in Abdominal Aortic Graft and Endograft Infections
- 2023
-
In: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 66:3, s. 397-406
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft-preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort.METHODS: Patients with abdominal AGI-related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for definition of AGI. Multivariable regression was performed to identify factors associated with mortality.RESULTS: A total of 169 patients with surgically treated abdominal AGI were identified, comprising 43 SC [14 endografts; 53% with a graft-enteric fistula (GEF) in total] and 126 RS [26 endografts; 50% with a GEF in total]. The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated 5-year survival for SC versus RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated 5-year survival for SC patients with a GEF versus without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC versus RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in 5-year survival comparing SC versus RS (HR 1.0, 95% CI 0.6 - 1.5).CONCLUSION: In this national AGI cohort, we could not identify any mortality difference comparing SC versus RS for AGI when adjusting for comorbidities. Presence of GEF likely negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC-treated patients.
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| 25. |
- Goel, Suchi, et al.
(author)
-
RIFINs are adhesins implicated in severe Plasmodium falciparum malaria
- 2015
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:4, s. 314-317
-
Journal article (peer-reviewed)abstract
- Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), bind to RBCs-preferentially of blood group A-to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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| 26. |
- Hammarlin, Mia-Marie, et al.
(author)
-
Digital (o)moral
- 2017
-
In: Sociala medier : Vetenskapliga perspektiv - Vetenskapliga perspektiv. - 9789140694805 ; , s. 55-66
-
Book chapter (other academic/artistic)
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| 27. |
- Hammarlin, Mia-Marie, et al.
(author)
-
Prat i text : Om skvaller som journalistisk metod
- 2017
-
In: Celebritetsskapande : Från Strindberg till Asllani - Från Strindberg till Asllani. - 9789198196177 - 9789198196795 ; 35, s. 93-93
-
Book chapter (peer-reviewed)
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| 28. |
- Hedström, Johanna, et al.
(author)
-
Quality of care in dysphagia patients: adaptation and validation of the Swedish SWAL-CARE questionnaire
- 2020
-
In: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 18:1
-
Journal article (peer-reviewed)abstract
- Background The aim of this study was to adapt the instrument and evaluate the psychometric properties of the Swedish version of the Swallowing Quality of Care questionnaire (S-SWAL-CARE) in patients with oropharyngeal dysphagia. Methods Translation and adaptation of the original SWAL-CARE into Swedish was performed according to established international guidelines. Field testing was performed using 100 patients with oropharyngeal dysphagia due to multiple reasons such as head and neck cancer and neurologic/neuromuscular disease, who had undergone swallowing evaluation within 6 months prior to the study. The patients answered the S-SWAL-CARE, the Quality from the Patient's Perspective (QPP) and the Swallowing Quality of Life (SWAL-QOL). Test-retest was performed in 20% of the participants. The reliability and validity of the S-SWAL-CARE were assessed by Pearson correlation coefficient and Cronbach's alpha as well as convergent and discriminative validity, respectively. Results The field testing of the S-SWAL-CARE resulted in sufficient reliability, with Cronbach's alpha values exceeding 0.90 for all domains. All items correlated strongly to their own domain, with weaker correlations to the other domains, indicating proper scale structure. Results also indicate sufficient convergent and discriminant validity when tested for association to the QPP domains and the SWAL-QOL Total score. The test-retest reliability of the S-SWAL-CARE demonstrated sufficient intraclass correlation coefficient (ICC) for the General advice domain (0.73) and Clinical advice domain (0.82). The ICC for the Patient satisfaction domain was lower (0.44). Conclusion The S-SWAL-CARE can be considered a reliable and valid tool to assess the dysphagia-related quality of care in a mixed Swedish dysphagia patient population.
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| 29. |
- Jacobs, Kevin B, et al.
(author)
-
Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 30. |
- Johansson, Karin, 1955-
(author)
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Reflektion, Insikt och Ansvar : Lärandet i att leva med diabetes
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- Aim: The overall aim is to develop knowledge about learning to live with diabetes.Methods: All four studies have been carried out within the caring science and using a life-world phenomenological approach. Study (I): data was collected through written narratives from seven patients with insulin treatment. Studies (II and III): data was collected through interviews with twelve patients with diabetes. Study (IV): Data was collected from four groups and two individual interviews with sixteen diabetes nurses. The method for the analysis can be described as a dialectic process, beginning with the whole, analyzing its parts, and then reconstructing the whole in order to understand the essence of the phenomenon.Main Findings: The result showed that patients’ experiences of the most obvious meanings of the phenomenon of being stricken by diabetes (I) are the fight against becoming your illness, a wish that everything would be as usual and that the new situation should only be natural. Furthermore, after having been diagnosed with the illness, the results demonstrated two themes that were particularly important in learning to live with diabetes. These were your own responsibility for gaining knowledge in order to incorporate the illness into your life and to find a balance between fear and control (II). As support for the learning (III), reflection over the learning and experiences has a crucial role for a new understanding of health processes. Insight into your own responsibility was a key factor for this reflection. To be able to give support (1V), the diabetes nurse must adopt a reflecting, self-critical attitude with an insight that the responsibility for learning lies with the patient and that the role for the diabetes nurse is to encourage and challenge the patient to self-reflection and taking responsibility on the basis of individual goals and pre-requisites.To give support in this way, the diabetes nurse must downplay the medical requirements for control and make more use of his/her medical competence to ask reflection-triggering questions based on a life-world perspective.Conclusion: Based on the patient’s life-world, an understanding is created that supports learning, which thereby can reduce the influence of the illness on the patient's life. This understanding makes it possible to incorporate the illness into the patient's life and create a balance between fear and control.
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| 31. |
- Kapoor, Pooja Middha, et al.
(author)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Journal article (peer-reviewed)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 32. |
- Källstrand, Johan, et al.
(author)
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Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome.
- 2010
-
In: Neuropsychiatric Disease and Treatment. - 1176-6328. ; 6, s. 289-296
-
Journal article (peer-reviewed)abstract
- Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD). In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs) elicited by forward masking in adults diagnosed with Asperger syndrome (AS). Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16), schizophrenic patients (n = 16) and attention deficit hyperactivity disorder patients (n = 16), respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005), which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking) may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases.
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| 33. |
- Källtorp, Mia, et al.
(author)
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Analysis of rat plasma proteins desorbed from gold and methyl- and hydroxyl-terminated alkane thiols on gold surfaces.
- 2000
-
In: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 11:3, s. 191-9
-
Journal article (peer-reviewed)abstract
- It is believed that adsorbed blood or plasma components, such as water, peptides, carbohydrates and proteins, determine key events in the concomitant inflammatory tissue response close to implants. The aim of the present study was to develop a procedure for the collection and analysis of minor amounts of proteins bound to solid metal implant surfaces. The combination of a sodium dodecyl sulfate washing method coupled with a polyacylamide gel electrophoretic protein separation technique (SDS-PAGE), Western blot and image analysis enabled the desorption, identification and semiquantification of specific proteins. The analyzed proteins were albumin, immunoglobulin G, fibrinogen and fibronectin. Concentration procedures of proteins were not required with this method despite the small area of the test surfaces. The plasma proteins were adsorbed to pure gold and hydroxylated and methylated gold surfaces, which elicit different tissue responses in vivo and plasma protein adsorption patterns in vitro. The image analysis revealed that the pure gold surfaces adsorbed the largest amount of total and specific proteins. This is in accordance with previous ellipsometry/antibody experiments in vitro. Further, the principles described for the protein analysis can be applied on implant surfaces ex vivo.
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| 34. |
- Lasselin, Julie, et al.
(author)
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Sleep during naturally occurring respiratory infections : A pilot study
- 2019
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 79, s. 236-243
-
Journal article (peer-reviewed)abstract
- There is strong experimental support that infections increase the drive for sleep in animals, and it is widely believed that more sleep is part of an adaptive immune response. While respiratory infections (RI) are very prevalent in humans, there is a striking lack of systematic knowledge on how it affects sleep. We recruited 100 people, among whom 28 became sick with an RI during the study period (fulfilling criteria for influenza-like illness, ILI, or acute respiratory infection, ARI). We measured sick participants' sleep at home, both objectively (actigraphy) and subjectively (diary ratings), for one week as well as four weeks later when healthy. During the week with RI, people spent objectively longer time in bed and had a longer total sleep time compared to the healthy week. During the infection, participants also had more awakenings, but no significant differences in sleep latency or sleep efficiency. While sick, people also reported increased difficulties falling asleep, worse sleep quality, more restless sleep and more shallow sleep, while they did not report sleep to be less sufficient. Most problems occurred at the beginning of the sickness week, when symptoms were strong, and showed signs of recovery thereafter (as indicated by interactions between condition and day/night of data collection for all the 10 sleep outcomes). The degree of symptoms of RI was related to a worse sleep quality and more restless sleep, but not to any of the objective sleep outcomes or the other subjective sleep variables. Having a higher body temperature was not significantly related to any of the sleep variables. This study suggests that having a respiratory infection is associated with spending more time in bed and sleeping longer, but also with more disturbed sleep, both objectively and subjectively. This novel study should be seen as being of pilot character. There is a need for larger studies which classify pathogen type and include baseline predictors, or that manipulate sleep, in order to understand whether the sleep alterations seen during infections are adaptive and whether sleep interventions could be used to improve recovery from respiratory infections.
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| 35. |
- Machiela, Mitchell J., et al.
(author)
-
Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
-
Journal article (peer-reviewed)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 36. |
- Machiela, Mitchell J, et al.
(author)
-
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 37. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(author)
-
Replication and fine mapping of ankylosing spondylitis replicated loci in the Swedish population reveal different CCHCR1 protective haplotypes
-
Other publication (other academic/artistic)abstract
- Background: The genetics of ankylosing spondylitis (AS) derives mainly from studies performed in large cohorts of British origin. However, within Europe, disease prevalence is higher in Sweden, and so we investigated the reproducibility of known AS susceptibility patterns in a homogeneous Swedish cohort.Methods: The replication power of the Swedish cohort was examined and a set of published SNP associations intersected with genotypes from an existing targeted sequencing study using these individuals (381 controls; 310 AS cases). To elucidate whether replication patterns derived from population subsampling or genetic similarity, allele frequency data from additional British and Swedish control populations were examined for genetic differentiation (FST). Replicated loci were fine mapped to investigate associations in more detail, and signals were dissected with haplotype analysis and functional annotation.Results: The study had 80% power to find variants of strong effect (Odds ratio, OR>2) given a wide range of risk allele frequencies (0.2-3), tagging HLA-B,CCHCR1and IL23R. The replication pattern was not due to European population genetic distance and fine mapping revealed genome-wide repositioned associations in HLA-Band CCHCR1, independent from the published associations (p-value < 2 x10-8, r2 < 0.3). The CCHCR1 locus showed two protective haplotype blocks (B1-1 and B2-1), independent from HLA-B signals (B1-1: r2 = 0.39, B2-2:r2=0.07), where 74% of controls were carrying 2 copies of the protective haplotypes (B1-1 and B2-1: OR=0.3, p-value = 1.2 x 10-45). Interestingly, while both haplotypes span CCHCR1, the effect of each haplotype is likely in cis, with eQTL evidence pointing to the regulation of TCF19(B1-1) and POU5F1(B1-2).Conclusions: Both European populations share key disease loci, but the Swedish cohort revealed fine-scale genetic differences, that may point to gene regulation. This study utilized a different variant resolution, and by doing so demonstrated that smaller populations have the potential to reveal new AS pathogenesis mechanisms and that further study of the Swedish population is warranted.
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| 38. |
- Mohamad, Kusdiantoro, et al.
(author)
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On the Origin of Indonesian Cattle
- 2009
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 4:5
-
Journal article (peer-reviewed)abstract
- Background: Two bovine species contribute to the Indonesian livestock, zebu (Bos indicus) and banteng (Bos javanicus), respectively. Although male hybrid offspring of these species is not fertile, Indonesian cattle breeds are supposed to be of mixed species origin. However, this has not been documented and is so far only supported by preliminary molecular analysis. Methods and Findings: Analysis of mitochondrial, Y-chromosomal and microsatellite DNA showed a banteng introgression of 10-16% in Indonesian zebu breeds. East-Javanese Madura and Galekan cattle have higher levels of autosomal banteng introgression (20-30%) and combine a zebu paternal lineage with a predominant (Madura) or even complete (Galekan) maternal banteng origin. Two Madura bulls carried taurine Y-chromosomal haplotypes, presumably of French Limousin origin. In contrast, we did not find evidence for zebu introgression in five populations of the Bali cattle, a domestic form of the banteng. Conclusions: Because of their unique species composition Indonesian cattle represent a valuable genetic resource, which potentially may also be exploited in other tropical regions.
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| 39. |
- Nyström, Anna-Maja, et al.
(author)
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Noonan and cardio-facio-cutanenous syndromes : two clinically and genetically overlapping disorders
- 2008
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:8, s. 500-506
-
Journal article (peer-reviewed)abstract
- Background: Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes PTPN11, SOS1, KRAS and RAF1. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: BRAF, KRAS, MEK1 and MEK2. Methods: A comprehensive mutation analysis of BRAF, KRAS, MEK1, MEK2 and SOS1 in 31 unrelated patients without mutations in PTPN11 is presented. Results: Mutations were identified in seven patients with CFC (two in BRAF, one in KRAS, one in MEK1, two in MEK2 and one in SOS1). Two mutations were novel: MEK1 E203Q and MEK2 F57L. The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC. We thus suggest involvement of BRAF in the pathogenesis of NS also. Conclusions: Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS–PTPN11-associated or CFC–BRAF-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.
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| 40. |
- Oldfors Hedberg, Carola, 1969, et al.
(author)
-
A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency.
- 2016
-
In: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 24:12, s. 1771-1777
-
Journal article (peer-reviewed)abstract
- We describe a new early-onset neuromuscular disorder due to a homozygous loss-of-function variant in the kyphoscoliosis peptidase gene (KY). A 7.5-year-old girl with walking difficulties from 2 years of age presented with generalized muscle weakness; mild contractures in the shoulders, hips and feet; cavus feet; and lordosis but no scoliosis. She had previously been operated with Achilles tendon elongation. Whole-body MRI showed atrophy and fatty infiltration in the calf muscles. Biopsy of the vastus lateralis muscle showed variability in fiber size, with some internalized nuclei and numerous very small fibers with variable expression of developmental myosin heavy chain isoforms. Some small fibers showed abnormal sarcomeres with thickened Z-discs and small nemaline rods. Whole-exome sequencing revealed a homozygous one-base deletion (c.1071delG, p.(Thr358Leufs*3)) in KY, predicted to result in a truncated protein. Analysis of an RNA panel showed that KY is predominantly expressed in skeletal muscle in humans. A recessive variant in the murine ortholog Ky was previously described in a spontaneously generated mouse mutant with kyphoscoliosis, which developed postnatally and was caused by dystrophy of postural muscles. The abnormal distribution of Xin and Ky-binding partner filamin C in the muscle fibers of our patient was highly similar to their altered localization in ky/ky mouse muscle fibers. We describe the first human case of disease associated with KY inactivation. As in the mouse model, the affected child showed a neuromuscular disorder - but in contrast, no kyphoscoliosis.
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| 41. |
- Ollila, Hanna M., et al.
(author)
-
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
-
Journal article (peer-reviewed)abstract
- Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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| 42. |
- Olsson, K., et al.
(author)
-
Cognitive Development in Single-Suture Craniosynostosis : A Systematic Review
- 2023
-
In: Developmental Neuropsychology. - : Taylor & Francis Group. - 8756-5641 .- 1532-6942. ; 48:5, s. 215-247
-
Research review (peer-reviewed)abstract
- There is conflicting evidence whether single-suture craniosynostosis (SSC), is linked to adversities of cognitive development. To assess the evidence for a link between SSC and cognition, a systematic literature search was conducted and eligible studies assessed for inclusion by two independent readers. Forty-eight studies met inclusion criteria. Small to medium but persistent effects on both general and some specific cognitive functions across age bands were found in higher quality studies for SSC overall. There was limited evidence for effects related to surgical correction. Methodologies varied substantially and there was a lack of longitudinal studies using broad assessment batteries.
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| 43. |
- Olsson, Mia, et al.
(author)
-
A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs
- 2011
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3, s. e1001332-
-
Journal article (peer-reviewed)abstract
- Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 x 10(-6), p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p, < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.
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| 44. |
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| 45. |
- Olsson, Mia, et al.
(author)
-
Evaluating person-centered care in neurological outpatient care : a mixed-methods content validity study
- 2024
-
In: BMC Nursing. - : BioMed Central Ltd.. - 1472-6955. ; 23:1
-
Journal article (peer-reviewed)abstract
- Background: Person-centered care (PCC) is gaining increased attention. PCC concerns the whole person behind the disease and can improve care for people with long-term conditions such as multiple sclerosis (MS) and Parkinson’s disease (PD). However, there is a lack of tools to assess PCC from the patients’ perspective, particularly in outpatient care. The Person-Centered Care instrument for outpatient care (PCCoc) is an instrument under development with the intention to fill this gap. The aim of this study was to test the user-friendliness and content validity of the PCCoc as experienced by persons with MS and PD in neurological outpatient care. Methods: Twenty persons with MS or PD completed the 35-item PCCoc followed by an interview regarding the instrument’s intelligibility and ease of use to assess its user-friendliness. Participants then rated the relevance of each item. These ratings were used to calculate the content validity index (CVI) for individual items (I-CVI) and for the overall scale (S-CVI). Results: It took a median of 5 min for participants to complete the PCCoc. Instrument instructions were found clear, items easy to understand, and response categories distinct. No important missing areas were reported. I-CVI values ranged between 0.75 and 1, and S-CVI was 0.96. Conclusions: We found support for the user-friendliness and content validity of the PCCoc among persons with MS and PD, suggesting that the PCCoc can be useful for evaluating and developing PCC in neurological outpatient care. Further testing in broader contexts, including psychometric testing, is warranted to establish its usefulness.
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| 46. |
- Olsson, Mia, et al.
(author)
-
Genome-Wide Analyses Suggest Mechanisms Involving Early B-cell Development in Canine IgA Deficiency
- 2015
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Journal article (peer-reviewed)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p <0.0005) to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p <0.0002) with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.
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| 47. |
- Olsson, Mia, et al.
(author)
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The dog as a genetic model for immunoglobulin A (IgA) deficiency : Identification of several breeds with low serum IgA concentrations
- 2014
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In: Veterinary Immunology and Immunopathology. - : Elsevier BV. - 0165-2427 .- 1873-2534. ; 60:3-4, s. 255-259
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Journal article (peer-reviewed)abstract
- Immunoglobulin A (IgA) serves as the basis of the secretory immune system by protecting the lining of mucosal sites from pathogens. In both humans and dogs, IgA deficiency (IgAD) is associated with recurrent infections of mucosal sites and immune-mediated diseases. Low concentrations of serum IgA have previously been reported to occur in a number of dog breeds but no generally accepted cut-off value has been established for canine IgAD. The current study represents the largest screening to date of IgA in dogs in terms of both number of dogs (n = 1267) and number of breeds studied (n = 22). Serum IgA concentrations were quantified by using capture ELISA and were found to vary widely between breeds. We also found IgA to be positively correlated with age (p < 0.0001). Apart from the two breeds previously reported as predisposed to low IgA (Shar-Pei and German shepherd), we identified six additional breeds in which > 10% of all tested dogs had very low (<0.07 g/l) IgA concentrations (Hovawart, Norwegian elkhound, Nova Scotia duck tolling retriever, Bullterrier, Golden retriever and Labrador retriever). In addition, we discovered low IgA concentrations to be significantly associated with canine atopic dermatitis (CAD, p < 0.0001) and pancreatic acinar atrophy (PAA, p = 0.04) in German shepherds.
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| 48. |
- Olsson, Mia, 1978-, et al.
(author)
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Thorough investigation of a canine autoinflammatory disease (AID) syndrome confirms one main risk factor and suggests a modifier locus for amyloidosis
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10, s. e75242-
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Journal article (peer-reviewed)abstract
- Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6x10(-8)) from each analysis showed that one haplotypic pair (H13-11) was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F-ST) distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05) renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts.
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| 49. |
- Olsson, Mia, 1978-
(author)
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Uncovering a Novel Pathway for Autoinflammation : With a Little Help from a Wrinkled Friend
- 2012
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Doctoral thesis (other academic/artistic)abstract
- A major challenge in medical genetics is to identify the mutations underlying heritable diseases. Dogs are excellent genetic models in the search for causative mutations, as they constitute a large library of naturally occurring heritable diseases many of which are analogous to those suffered by man. In addition, these animals have a genome structure well suited to gene mapping. The Shar-Pei dog has two breed-specific features; a strongly selected for wrinkled skin and a high predisposition to an autoinflammatory disease (AID). Abnormalities in the innate immune system cause this type of disease, presenting as spontaneous attacks of inflammation. Persistent inflammation puts an affected Shar-Pei at risk of amyloidosis, organ failure and premature death. In humans, similar AIDs occur and for a majority of cases, no underlying genetic cause has yet been identified. The aim of this thesis was to use the Shar-Pei as a genetic model for autoinflammation in order to find new genes and signalling pathways involved in disease. In paper I, a pleiotropic mutation was identified that could explain both the wrinkled skin and autoinflammation in Shar-Pei. The mutation is associated with an up-regulation of Hyaluronic Acid Synthase 2 (HAS2). Increased expression of HAS2 leads to abnormal depositions of hyaluronic acid (HA) in the skin, resulting in the wrinkled appearance. When fragmented, HA also function as a damage signal sensed by the innate immune system which then responds with inflammation. By selecting for the wrinkled skin, the autoinflammatory disease has inadvertently been enriched in the breed. In paper II, five different inflammatory signs could be associated with the same genetic risk factor, allowing the introduction of a new terminology: Shar-Pei autoinflammatory disease (SPAID) to describe the whole disease complex. In addition, a modifying locus containing several biologically attractive genes was suggested to contribute to varying incidence of amyloidosis in Shar-Pei. In paper III, signs of pathological changes in HA metabolism were investigated in human AID. HA concentration was found to be both higher in subjects with no molecular diagnosis and also associated to disease activity and severity. Taken together, this suggests HA is also involved in human AID.
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| 50. |
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