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2.
  • Allard, Christina, et al. (författare)
  • Rasbiologiskt språkbruk i statens rättsprocess mot sameby
  • 2015
  • Ingår i: Dagens Nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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  • Hagell, Peter, et al. (författare)
  • Apomorphine formulation influences subcutaneous complications in continuous apomorphine pump therapy for Parkinson’s disease
  • 2017
  • Ingår i: Movement Disorders.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: To explore if the occurrence and severity of subcutaneous (sc) nodules is influenced by the pharmaceutical formulation of apomorphine used for sc infusion in advanced Parkinson’s disease (PD).Background: Apomorphine infusion is an effective therapy in advanced PD, but a limitation is troublesome sc nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal clinical experience has suggested that shifting from one of these (Apo-Go PumpFill; apoGPF) to another (Apomorphine PharmSwed; apoPS, developed in Sweden) may influence the occurrence and severity of sc nodules.Methods: In this multicenter open-label prospective observational study, 15 people with advanced PD (mean PD- duration, 13.4 years; median Hoehn & Yahr, IV) on apoGPF since a mean of 2.1 years and with troublesome sc nodules were switched to apoPS. Ongoing interventions to treat existing nodules (ultrasound, massage, Hirudoid cream) continued, and apomorphine as well as other drugs was managed according to clinical routines. Data were collected between May 2015 and March 2017; at baseline, at the time of switching (about 2 weeks later), and up to 1.7-4.2 (mean, 2.5) months post-switch follow-up. Primary outcomes were total nodule numbers, size (mm diameter for the 5 worst nodules), consistency (scored 0-3 for the 5 worst nodules), and associated skin changes (scored 0-4 for the 5 worst nodules) and pain (scored 0-5). Patients also rated their perceived PD severity and motor complications (UPDRS IV). Patient preferences 5-12 months post-switch (2-9 months after follow-up) were also recorded.Results: Apomorphine and L-dopa doses did not change over the observation period (P≥0.400). Baseline nodule numbers (7.4 vs. 4.6; P<0.003), size (92.9 vs. 54.1 mm; P=0.016), consistency (11 vs. 5; P=0.003), skin changes (3 vs. 1.5; P=0.205), and average pain (1 vs. 0; P=0.020) improved 11 weeks post-switch. Patient-reported PD severity (P=0.020) and motor fluctuations improved (P=0.051), whereas dyskinesias tended to increase (P=0.205). At 5-12 months post-switch, 13 patients had decided to remain on apoPS; mainly due to improved nodules.Conclusions: These observations suggest that apoPS may have a better safety profile compared to apoGPF in terms of sc nodule occurrence and severity. There is a need for larger, randomized controlled studies for firmer conclusions.
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5.
  • Hagell, Peter, et al. (författare)
  • Apomorphine formulation influences subcutaneous complications in continuous apomorphine pump therapy for Parkinson’s disease
  • 2017
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: To explore if the occurrence and severity of subcutaneous (sc) nodules is influenced by the pharmaceutical formulation of apomorphine used for sc infusion in advanced Parkinson’s disease (PD). Background: Apomorphine infusion is an effective therapy in advanced PD, but a limitation is troublesome sc nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal clinical experience has suggested that shifting from one of these (Apo-Go PumpFill; apoGPF) to another (Apomorphine PharmSwed; apoPS, developed in Sweden) may influence the occurrence and severity of sc nodules. Methods: In this multicenter open-label prospective observational study, 15 people with advanced PD (mean PD- duration, 13.4 years; median Hoehn & Yahr, IV) on apoGPF since a mean of 2.1 years and with troublesome sc nodules were switched to apoPS. Ongoing interventions to treat existing nodules (ultrasound, massage, Hirudoid cream) continued, and apomorphine as well as other drugs was managed accordingto clinical routines. Data were collected between May 2015 and March 2017; at baseline, at the time of switching (about 2 weeks later), and up to 1.7-4.2 (mean, 2.5) months post-switch follow-up. Primary outcomes were total nodule numbers, size (mm diameter for the 5 worst nodules), consistency (scored 0-3 for the 5 worst nodules), and associated skin changes (scored 0-4 for the 5 worst nodules) and pain (scored 0-5). Patients also rated their perceived PD severity and motor complications (UPDRS IV). Patient preferences 5-12 months post-switch (2-9 months after follow-up) were also recorded. Results: Apomorphine and L-dopa doses did not change over the observation period (P≥0.400). Baseline nodule numbers (7.4 vs. 4.6; P<0.003), size (92.9 vs. 54.1 mm; P=0.016), consistency (11 vs. 5; P=0.003), skin changes (3 vs. 1.5; P=0.205), and average pain (1 vs. 0; P=0.020) improved 11 weeks post-switch. Patient-reported PD severity (P=0.020) and motor fluctuations improved (P=0.051), whereas dyskinesias tended to increase (P=0.205). At 5-12 months post-switch, 13 patients had decided to remain on apoPS; mainly due to improved nodules. Conclusions: These observations suggest that apoPS may have a better safety profile compared to apoGPF in terms of sc nodule occurrence and severity. There is a need for larger, randomized controlled studies for firmer conclusions.
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  • Andersson, Lena, 1965-, et al. (författare)
  • Respiratory health and inflammatory markers : Exposure to respirable dust and quartz and chemical binders in Swedish iron foundries
  • 2019
  • Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 14:11
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To study the relationship between respirable dust, quartz and chemical binders in Swedish iron foundries and respiratory symptoms, lung function (as forced expiratory volume FEV1 and vital capacity FVC), fraction of exhaled nitric oxide (FENO) and levels of club cell secretory protein 16 (CC16) and CRP.METHODS: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Full shift sampling and examination were performed on the second or third day of a working week after a work free weekend, with additional sampling on the fourth or fifth day. Logistic, linear and mixed model analyses were performed including, gender, age, smoking, infections, sampling day, body mass index (BMI) and chemical binders as covariates.RESULTS: The adjusted average respirable quartz and dust concentrations were 0.038 and 0.66 mg/m3, respectively. Statistically significant increases in levels of CC16 were associated with exposure to chemical binders (p = 0.05; p = 0.01) in the regression analysis of quartz and respirable dust, respectively. Non-significant exposure-responses were identified for cumulative quartz and the symptoms asthma and breathlessness. For cumulative chemical years, non-significant exposure-response were observed for all but two symptoms. FENO also exhibited a non significant exposure-response for both quartz and respirable dust. No exposure-response was determined for FEV1 or FVC, CRP and respirable dust and quartz.CONCLUSIONS: Our findings suggest that early markers of pulmonary effect, such as increased levels of CC16 and FENO, are more strongly associated with chemical binder exposure than respirable quartz and dust in foundry environments.
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8.
  • Andersson, Staffan, et al. (författare)
  • Effect of storage time and temperature on stability of bioactive compounds in aseptically packed beverages prepared from rose hips and sea buckthorn berries
  • 2015
  • Ingår i: Agricultural and Food Science. - 1795-1895 .- 1459-6067. ; 24:4, s. 273-288
  • Tidskriftsartikel (refereegranskat)abstract
    • Rose hips and sea buckthorn berries contain high amounts of beneficial bioactive compounds. In this study the content and stability of natural vitamins and antioxidants were investigated in two fruit beverages made from rose hip powder, sea buckthorn berry puree and white grape juice concentrate, and wheat germ oil in one of the beverages. Beverages were formulated, pasteurised and filled aseptically in Tetra Brik packages and stored up to 35 days at 4 degrees C or 22 degrees C. Samples were analysed for the content of ascorbic acid, carotenoids, major phenolics, tocochromanols, total phenols and total antioxidant capacity as ferric reducing ability. The largest changes occurred during the first 5 days of storage, thereafter mainly ascorbic acid decreased. In the wheat germ oil supplemented beverage, alpha-tocopherol was more rapidly degraded. Negative correlations between the decrease of some carotenoids and tocochromanols, and the increase of some phenolics, suggest relationships of redox reactions specific to the amount of oil supplemented. From the present study we can conclude that additions of oil to beverages should be carefully selected to avoid oxidations of bioactive compounds. Furthermore, packaging of the beverages should be carried out at higher temperatures and thereafter it should be stored at low temperatures (4 degrees C), which decreased oxidation of all bioactive compounds except ascorbic acid.
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9.
  • Asker, Martin, et al. (författare)
  • Risk factors for, and prevention of, shoulder injuries in overhead sports : a systematic review with best-evidence synthesis.
  • 2018
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:20, s. 312-1319
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVE: To assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports.DESIGN: Systematic review with best-evidence synthesis.DATA SOURCES: Medline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017.ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria.RESULTS: Of 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power.CONCLUSIONS: All investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports.PROSPERO TRIAL REGISTRATION NUMBER: CRD42015026850.
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  • Bhoo-Pathy, Nirmala, et al. (författare)
  • Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
  • 2015
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR = 0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; P-trend = 0.029. While there was no significant effect modification by hormone receptor status (P = 0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P = 0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR = 0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (P-trend = 0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR = 0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.
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  • Björkander, Sophia, et al. (författare)
  • Staphylococcus aureus-derived factors induce IL-10, IFN-gamma and IL-17A-expressing FOXP3(+)CD161(+) T-helper cells in a partly monocyte-dependent manner
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells. Stimulation of PBMC with S. aureus 161:2-cell free supernatant (CFS) induced expression of IL-10, IFN-gamma and IL-17A in FOXP3(+) cells. Further, CD161 and HELIOS separated the FOXP3(+) cells into four distinct populations regarding cytokine-expression. Monocyte-depletion decreased S. aureus 161:2-induced activation of FOXP3(+) cells while pre-stimulation of purified monocytes with S. aureus 161:2-CFS and subsequent co-culture with autologous monocyte-depleted PBMC was sufficient to mediate activation of FOXP3(+) cells. Together, these data show that S. aureus potently induces FOXP3(+) cells and promotes a diverse phenotype with expression of regulatory and pro-inflammatory cytokines connected to increased CD161-expression. This could indicate potent regulation or a contribution of FOXP3(+) cells to inflammation and repression of immune-suppression upon encounter with S. aureus.
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  • Haby, Lena, et al. (författare)
  • Optimizing yield and quality in malting barley by the governance of field cultivation conditions
  • 2018
  • Ingår i: Journal of Cereal Science. - : Elsevier BV. - 0733-5210 .- 1095-9963. ; 82, s. 230-242
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluates how cultivation location, year, soil conditions and starter fertilizer interact and determine yield and quality of malting barley. Size exclusion high performance liquid chromatography (SE-HPLC) was applied to determine protein composition in mature and malted barley.The effects of starter fertilizer treatments on yield and quality of malting barley was largely hidden by the impact of growing location and cultivation year on these parameters. Here, the highest yield and the lowest grain protein concentration was found in samples cultivated on sandy soil with adequate precipitation and a relatively low soil temperature (below 15-17 degrees C) during grain filling. In malted grains, the general change in protein composition as related to mature grains, was a decrease in the polymerized protein fractions and an increase in the more easily extractable and smaller proteins. However, cultivation conditions impacted the changes of the protein fractions; the highest break-down rates of polymerized proteins was found for samples cultivated on sandy soil with enough precipitation and a relatively low soil temperature (below 15-17 degrees C) during grain filling. Thus, the sandy soil, enough precipitation and relatively low soil temperature were the most beneficial both for grain yield and for protein based quality of the malting barley.
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17.
  • Hannuksela, Matias, et al. (författare)
  • A novel variant in MYLK causes thoracic aortic dissections : genotypic and phenotypic description
  • 2016
  • Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mutations in MYLK cause non- syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.Methods: We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers.Results: Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_ 3273del, p. Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation.Conclusions: Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.
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  • Hannuksela, Matias, 1969- (författare)
  • Familial thoracic aortic aneurysms and dissections : studies on genotype and phenotype
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Thoracic aortic aneurysms and dissections (TAAD) have a genetic component with an estimated 20-25% of the patients having a positive family history. An aneurysm often precedes a dissection. Acute aortic dissections are associated with high mortality and morbidity, even when operated on. Complications due to prophylactic surgery are considerably fewer. Therefore, patients at risk for dissection should be identified, followed-up and evaluated for prophylactic intervention.Aims: 1. To establish reference values for ascending (AoA) and descending aortic (AoD) diameters measured by computed tomography. 2. To study the effectiveness of phenotypic cascade screening in families with an inherited form of thoracic aortic aneurysms and dissections (FTAAD) and to address questions that arise when screening for a genetic disorder is applied. 3. To study the agreement of aortic diameters obtained by TTE and MRI and to study aortic stiffness in individuals from families with FTAAD. 4. To perform exome sequencing in order to identify pathogenic sequence variants causing FTAAD, to characterize the phenotype, and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.Results: Paper I: The diameter of the thoracic aorta increased by 0.17 mm (0.12 – 0.20 mm) per year. The mean sex-related difference in diameter was 1.99 mm (1.28 – 2.60 mm) with men having larger aortas than women. The mean difference in aortic diameter per unit BMI was 0.27 mm (0.14 – 0.44 mm). Upper normal limits for the AoA can be calculated by the formula D (mm)=31+0.16*age and for the AoD by D (mm)=21+0.16*age.Paper II: Of 106 individuals from families with FTAAD but without known thoracic aortic disease, 19 individuals (18%) were identified to have a dilated AoA. The expected number of individuals in this group with an autosomal dominant disease would have been 40 (p<0.0001). In first-degree relatives younger than 40, we found only one individual with a dilated aorta although the expected number of individuals with disease causing mutation would have been 10.Paper III: Of 116 individuals investigated, 21 were identified with thoracic aortic dilatation and 95 individuals with normal thoracic aortic diameter. Aortic stiffness increased with age and diameter. The individuals with aortic dilatation were older than those without (49 vs. 37 years, p=0.001) and showed lower aortic elastic properties. The diameters measured by TTE and MRI correlated strongly (r2=0.93). The mean difference in diameters between the two methods was 0.72 mm (95% CI 0.41-1.02) with TTE giving larger diameters than MRI.Paper IV: From exome sequencing and segregation analysis, a 2-bp deletion in the MYLK gene (c.3272_3273del) was identified to cause FTAAD. The age and the aortic diameter at dissection or rupture varied in the family members. We did not find any differences in aortic diameter, aortic stiffness, or pulse wave velocity between carriers and non-carriers.Conclusions: Thoracic aortic diameter increases with age, and sex and body size are also associated with the diameter. In FTAAD, screening identifies family members with a previously unknown aortic dilatation. However, a normal aortic diameter does not exclude an individual from being a carrier of FTAAD. TTE can be used in follow-up for the ascending aorta. Individuals identified to have a dilated thoracic aorta have increased aortic stiffness compared to individuals with normal thoracic aortic diameter. The MYLK mutation (c.3272_3273del) causes thoracic aortic dissections with variable clinical expression. No differences in aortic stiffness were identified between MYLK mutation carriers and non-carriers.
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  • Hannuksela, Matias, et al. (författare)
  • Screening for familial thoracic aortic aneurysms with aortic imaging does not detect all potential aarriers of the disease
  • 2015
  • Ingår i: Aorta. - : Georg Thieme Verlag KG. - 2325-4637. ; 3:1, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: About 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have a first-degree relative with a similar disease. The familial form (FTAAD) of the disease is inherited in an autosomal-dominant pattern. Current guidelines for thoracic aortic disease recommend screening of first-degree relatives of TAAD patients. In known familial disease, screening of both first- and second-degree relatives is recommended. However, the outcomes of such a screening program are unknown.Methods: We screened all first- and second-degree relatives in seven families with known FTAAD with echo- cardiography. No underlying gene defect had been detected in these families.Results: Of 119 persons investigated, 13 had known thoracic aortic disease. In the remaining 106 cases, we diagnosed 19 additional individuals with a dilated ascending thoracic aorta; for an autosomal-dominant disease, the expected number of individuals in this group would have been 40 (p<0.0001). Further, only one of the 20 first-degree relatives younger than 40 years had a dilated aorta, although the expected number of individuals with a disease-causing mutation would have been 10.Conclusions: In most families with TAAD, a diagnosis still relies on measuring the diameter of the thoracic aorta. We show that a substantial number of previously unknown cases of aortic dilatation can be identified by screening family members. It is, however, not possible to consider anyone free of the condition, even if the aortic diameter is normal, especially at a younger age.
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  • Johansson, Ewa-Lena, et al. (författare)
  • Doftöverkänslighet : sensorisk hyperreaktivitet i luftvägarna
  • 2016
  • Bok (populärvet., debatt m.m.)abstract
    • Kemisk överkänslighet innebär att man får hälsobesvär av vissa dofter och kemikalier. Utlösande faktorer kan till exempel vara parfym, blomdoft, rök eller rengöringsprodukter. De drabbade reagerar betydligt kraftigare än vad som är normalt redan vid låga doser som inte anses skadliga eller toxiska.Det finns en särskild grupp av personer som får luftvägsbesvär av dofter och kemikalier. I dagligt tal kallar vi det doftöverkänslighet. Inom vården används begreppet sensorisk hyperreaktivitet, SHR, för detta tillstånd. Ungefär sex procent av befolkningen uppfyller kriterierna för diagnos.I den här kunskapssammanställningen belyses epidemiologi, trolig patofysiologi, utredning och behandlingsmöjligheter av SHR ur olika aspekter. Den är främst ämnad för dig som i din yrkesroll kommer i kontakt med patienter med SHR, men rekommenderas till alla med särskilt intresse för området.
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21.
  • Johansson, Ewa-Lena, et al. (författare)
  • Physical Therapy Treatment of Impaired Chest Mobility in Patients with Airway Sensory Hyperreactivity
  • 2017
  • Ingår i: Physiotherapy Research International. - : Wiley. - 1358-2267. ; 22:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose. In sensory hyperreactivity (SHR), patients have symptoms from the airways and the chest induced by environmental irritants like scenting products and cigarette smoke. They are characterized by increased cough reaction to inhaled capsaicin compared with healthy controls. Lung function tests are normal, and asthma medications have no or little effect. In a recent published article, patients with SHR were found to have impaired chest mobility and increased pain sensitivity. The purpose of this study was to evaluate if a physiotherapeutic intervention can increase chest mobility in SHR, influence these patients' symptoms and reduce capsaicin cough sensitivity. Methods. Forty-one SHR patients were initially randomized in to groups, one for training and one for symptom registration in this controlled training study. It consisted of a daily training programme containing simple movements to increase the flexibility of the chest, a breathing exercise and a relaxation session as well as symptom registration. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using pressure algometry and a standardized capsaicin inhalation threshold provocation-evaluated cough sensitivity. Results. Twenty seven patients were left for analyses after 12 weeks and 26 patients after 24 weeks. Chest mobility and upper thoracic respiratory movements improved (p<0.01), feeling of chest pressure and the capsaicin cough sensitivity decreased (p<0.01). The patients also showed of significantly lowered pain pressure thresholds measured with algometry, compared with healthy controls (p<0.001). Conclusion. Improvement of chest mobility after physiotherapeutic intervention indicates that these patients may have acquired a dysfunctional breathing pattern. The regular use of a training programme and structural breathing instructions can be used to improve chest mobility, chest symptoms and capsaicin cough sensitivity in patients with SHR and signs of dysfunctional breathing. Copyright (C) 2016 John Wiley & Sons, Ltd.
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22.
  • Johansson, Ewa-Lena, et al. (författare)
  • Small and large airway reactions to osmotic stimuli in asthma and chronic idiopathic cough
  • 2018
  • Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1094-5539. ; 49, s. 112-118
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic cough is a common symptom and related to several pulmonary, airway and heart diseases. When all likely medical explanations for the coughing are excluded, there remains a large group of patients with chronic coughing, which is mostly a cough reflex easily triggered by environmental irritants and noxious stimuli. The main aim of this study was to improve the diagnostic ability to differentiate chronic idiopathic cough (CIC) from asthma. Methods: Twenty-three patients with CIC, 16 patients with mild asthma and 21 control participants were included. The study consisted of three randomised bronchial provocations with osmotic stimuli: mannitol, eucapnic dry air and hypertonic saline. At each provocation lung function was assessed by spirometry and impulse oscillometry (IOS). Results: In a comparison of the groups, while the FEV1 measurements did not differ, the CIC group had increased airway resistance and reactance after provocation with hypertonic saline compared to the control subjects. After mannitol provocation the patients with asthma had significantly increased airway resistance compared to the controls and from eucapnic dry air provocations these patients had a significant reduction in spirometry values and increased airway resistance compared to both the patients with CIC and the controls. Conclusion: The asthma group reacted in a predictable way with impaired lung function from osmotic provocations, whereas the patients with CIC demonstrated peripheral airway changes from hypertonic saline, also known to be a noxious stimulus. The IOS method uncovers differences between patients with CIC and control participants that contribute to our ability to provide a correct diagnosis.
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23.
  • Johansson, Ewa-Lena, et al. (författare)
  • Small and large airways' reactions to inhaled capsaicin in patients with chronic idiopathic cough, or asthma and in healthy control subjects
  • 2019
  • Ingår i: Experimental Lung Research. - : Informa UK Limited. - 0190-2148 .- 1521-0499. ; 45:3-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Cough is a common medical problem, and when it persists for more than 8 weeks it is arbitrarily defined as chronic. While spirometry assesses the large airways, impulse oscillometry system (IOS) measures peripheral airway function. The present study investigated whether provocation with inhaled capsaicin affects the large and small airways in patients with chronic idiopathic cough (CIC) or asthma and in healthy controls. Materials and methods: Twenty-one patients with CIC, 18 patients with asthma, and 22 healthy controls were subjected to a provocation with capsaicin, and lung function was assessed by IOS and spirometry. Results: At baseline, before the capsaicin provocation, the CIC group had significantly increased airway resistance compared to the controls. After capsaicin provocation, the CIC group exhibited a significant increase in total airway resistance. The asthma group showed a small but significant reduction in spirometry, increased airway resistance, and reactance after capsaicin provocation. Capsaicin inhalation affected neither the spirometry nor the IOS of the healthy controls. Conclusions: The present study demonstrates that inhaled capsaicin induces changes in lung function, both in patients with CIC and in patients with asthma, when IOS, which measures changes also in the peripheral airways, is used. IOS appears to be a more sensitive tool than spirometry for the detection of airway impairment in airway provocation studies. In patients with CIC, higher peripheral resistance at baseline may have clinical significance.
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24.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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25.
  • Menard, Julien A., et al. (författare)
  • Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis
  • 2016
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 76:16, s. 4828-4840
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo. On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential.
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26.
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27.
  • Romieu, Isabelle, et al. (författare)
  • Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition : Short title
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:8, s. 1921-1930
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption. What's new? Although it is now established that alcohol consumption increases breast cancer risk, many questions remain. Using a prospective study design with 11,576 incident breast cancer cases across 10 European countries, the authors confirmed the increased risk of alcohol on breast cancer development. They further show that women who started drinking before their first full-term pregnancy have a higher risk than women who started afterwards. These effects were observed in hormone-receptor positive and -negative tumors pointing to non-hormonal pathways that need to be further investigated.
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28.
  • Romieu, Isabelle, et al. (författare)
  • Fiber intake modulates the association of alcohol intake with breast cancer
  • 2017
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:2, s. 316-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35–70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person-years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (<18.5 g/day), the risk of BC per 10 g/day of alcohol intake was 1.06 (1.03–1.08) while among subjects with high intake of fiber (>24.2 g/day) the risk of BC was 1.02 (0.99–1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber-rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (<18.5 g/day) had the highest risk for BC. Specific benefits were associated with fibers from vegetable, warranting further investigations into specific fiber sources and their mechanistic interactions with alcohol-induced BC risk.
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29.
  • Skogby, Sandra, 1989, et al. (författare)
  • Borttappad i vården
  • 2018
  • Ingår i: Nationella utbildningsdagar för vårdprofessioner inom kardiologi VIC - Medfödda hjärtfel "Vårdens framgångar ger nya möjligheter och utmaningar".
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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30.
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31.
  • Stattin, Eva-Lena, et al. (författare)
  • A novel ECEL1 mutation expands the phenotype of distal arthrogryposis multiplex congenita type 5D to include pretibial vertical skin crease
  • 2018
  • Ingår i: American Journal of Medical Genetics. Part A. - : WILEY. - 1552-4825 .- 1552-4833. ; 176:6, s. 1405-1410
  • Tidskriftsartikel (refereegranskat)abstract
    • Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder characterized by multiple joint contractures often in association with other congenital abnormalities. Pretibial linear vertical creases are a rare finding associated with arthrogryposis, and the etiology of the specific condition is unknown. We aimed to genetically and clinically characterize a boy from a consanguineous family, presenting with AMC and pretibial vertical linear creases on the shins. Whole exome sequencing and variant analysis revealed homozygous novel missense variants of ECEL1 (c.1163T > C, p.Leu388Pro, NM_004826) and MUSK (c.2572C > T, p.Arg858Cys, NM_005592). Both variants are predicted to have deleterious effects on the protein function, with amino acid positions highly conserved among species. The variants segregated in the family, with healthy mother, father, and sister being heterozygous carriers and the index patient being homozygous for both mutations. We report on a unique patient with a novel ECEL1 homozygous mutation, expanding the phenotypic spectrum of Distal AMC Type 5D to include vertical linear skin creases. The homozygous mutation in MUSK is of unknown clinical significance. MUSK mutations have previously shown to cause congenital myasthenic syndrome, a neuromuscular disorder with defects in the neuromuscular junction.
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32.
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33.
  • Ternesten-Hasséus, Ewa, 1956, et al. (författare)
  • Cough reduction using capsaicin
  • 2015
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 109:1, s. 27-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain. Objectives: We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing. Methods: Twenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms. Results: Three patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (p < 0.020) and in controls (p < 0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p < 0.0004) and C5 (p < 0.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (p < 0.0030) compared to the baseline scores. Conclusion: Capsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1). (C) 2014 The Authors. Published by Elsevier Ltd.
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34.
  • Trägårdh, Elin, et al. (författare)
  • Evaluation of inter-departmental variability of ejection fraction and cardiac volumes in myocardial perfusion scintigraphy using simulated data
  • 2015
  • Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial perfusion scintigraphy (MPS) is a clinically useful noninvasive imaging modality for diagnosing patients with suspected coronary artery disease. By utilizing gated MPS, the end diastolic volume (EDV) and end systolic volume (ESV) can be measured and the ejection fraction (EF) calculated, which gives incremental prognostic value compared with assessment of perfusion only. The aim of this study was to evaluate the inter-departmental variability of EF, ESV, and EDV during gated MPS in Sweden.Methods: Seventeen departments were included in the study. The SIMIND Monte Carlo (MC) program together with the XCAT phantom was used to simulate three patient cases with different EDV, ESV, and EF. Individual simulations were performed for each department, corresponding to their specific method of performing MPS. Images were then sent to each department and were evaluated according to clinical routine. EDV, ESV, and EF were reported back.Results: There was a large underestimation of EDV and ESV for all three cases. Mean underestimation for EDV varied between 26% and 52% and for ESV between 15% and 60%. EF was more accurately measured, but mean bias still varied between an underestimation of 24% to an overestimation of 14%. In general, the intra-departmental variability for EDV, ESV, and EF was small, whereas inter-departmental variability was larger.Conclusions: Left ventricular volumes were generally underestimated, whereas EF was more accurately estimated. There was, however, large inter-departmental variability.
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35.
  • Westberg, Håkan, 1949-, et al. (författare)
  • Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz
  • 2019
  • Ingår i: International Archives of Occupational and Environmental Health. - : Springer Berlin/Heidelberg. - 0340-0131 .- 1432-1246. ; 92:8, s. 1087-1098
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To study the relationship between inhalation of airborne particles and quartz in Swedish iron foundries and markers of inflammation and coagulation in blood.METHODS: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Stationary measurements were used to study the concentrations of respirable dust and quartz, inhalable and total dust, PM10 and PM2.5, as well as the particle surface area and the particle number concentrations. Markers of inflammation, namely interleukins (IL-1β, IL-6, IL-8, IL-10 and IL-12), C-reactive protein, and serum amyloid A (SAA) were measured in plasma or serum, together with markers of coagulation including fibrinogen, factor VIII (FVIII), von Willebrand factor and D-dimer. Complete sampling was performed on the second or third day of a working week after a work-free weekend, and follow-up samples were collected 2 days later. A mixed model analysis was performed including sex, age, smoking, infections, blood group, sampling day and BMI as covariates.RESULTS: The average 8-h time-weighted average air concentrations of respirable dust and quartz were 0.85 mg/m3 and 0.052 mg/m3, respectively. Participants in high-exposure groups with respect to some of the measured particle types exhibited significantly elevated levels of SAA, fibrinogen and FVIII.CONCLUSIONS: These observed relationships between particle exposure and inflammatory markers may indicate an increased risk of cardiovascular disease among foundry workers with high particulate exposure.
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36.
  • Wilbe, Maria, et al. (författare)
  • A novel approach using long-read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders
  • 2017
  • Ingår i: Prenatal Diagnosis. - : Wiley. - 0197-3851 .- 1097-0223. ; 37:11, s. 1146-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveDe novo mutations contribute significantly to severe early-onset genetic disorders. Even if the mutation is apparently de novo, there is a recurrence risk due to parental germ line mosaicism, depending on in which gonadal generation the mutation occurred.MethodsWe demonstrate the power of using SMRT sequencing and ddPCR to determine parental origin and allele frequencies of de novo mutations in germ cells in two families whom had undergone assisted reproduction.ResultsIn the first family, a TCOF1 variant c.3156C>T was identified in the proband with Treacher Collins syndrome. The variant affects splicing and was determined to be of paternal origin. It was present in <1% of the paternal germ cells, suggesting a very low recurrence risk. In the second family, the couple had undergone several unsuccessful pregnancies where a de novo mutation PTPN11 c.923A>C causing Noonan syndrome was identified. The variant was present in 40% of the paternal germ cells suggesting a high recurrence risk.ConclusionsOur findings highlight a successful strategy to identify the parental origin of mutations and to investigate the recurrence risk in couples that have undergone assisted reproduction with an unknown donor or in couples with gonadal mosaicism that will undergo preimplantation genetic diagnosis.
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