| 1. |
- Helgadottir, Anna, et al.
(författare)
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Genome-wide analysis yields new loci associating with aortic valve stenosis
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
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| 2. |
- Kågedal, Bertil, 1943-, et al.
(författare)
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Determination of glomerular filtration rate, a spin off aftercontrast-enhanced computed tomography among criticallyill patients − proof of concept
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background Recently, Gong et al. (Gong et al. 2022) showed, in nine heathy subjects, that plasma clearance of high doses of iohexol given as contrast enhanced computed tomography (CT) could be used for determination of glomerular filtration rate (GFR). We utilized high doses of iohexol from angiographic or other contrast enhanced CT given to critical ill patients for calculation of GFRiohexol and compared these data with standard low dose iohexol GFR determinations.Method Patients at intensive care units (ICUs) in Southeast Sweden intended for radiographic investigations that included injection of 45-120 ml of iohexol (Omnipaque) were included, and the concentration of iohexol in plasma was measured by HPLC. Iohexol clearance was calculated by the method of Bröchner-Mortensen. The following days was iohexol clearance determined using the standard low dose of 5 mL of iohexol. Sixteen patients admitted to ICUs were included in this pilot study.Results GFR after high dosing of iohexol at contrast enhanced CT could be measured for all sixteen critically ill patients. Patients with normal or increased renal function had neglectable iohexol concentrations the day following the CT scan. There was excellent correlation between GFR determination with high and standard low iohexol dosing among these 6 patients. Ten patients had decreased renal function and delayed elimination of iohexol, thus was not GFR measurement with low dose iohexol possible to analyse the day after CT scan with high dose iohexol.Conclusion This pilot study showed that GFR can be measured after high doses of iohexol at enhanced CT and compare well with the standard low dose of iohexol clearance determinations.
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| 3. |
- Oskarsson, Viktor, et al.
(författare)
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Rising incidence of acute pancreatitis in Sweden : National estimates and trends between 1990 and 2013
- 2020
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Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 8:4, s. 472-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent reports from western countries have indicated an increased incidence and a decreased mortality in acute pancreatitis. However, the incidence assessment has often been hampered by the inclusion of both first-time and recurrent episodes of acute pancreatitis.Methods: In this retrospective cohort study, all Swedish residents hospitalized with a first-time episode of acute pancreatitis between 1990 and 2013 were identified using national registers. Sex- and age-standardized incidence rates per 100,000 individuals and year were calculated, as were annual percent changes (APC) from joinpoint regression models.Results: Overall, between 1990 and 2013, 66,131 individuals had a first-time episode of acute pancreatitis in Sweden. Comparing the first five years (1990-1994) to the last four years (2010-2013) of the study period, the overall incidence of acute pancreatitis increased from 25.2 (95% confidence interval (CI): 24.1, 26.3) to 38.3 (95% CI: 37.0, 39.5) cases per 100,000 individuals and year. An increase in incidence was observed irrespective of the subtypes of acute pancreatitis as well as the sex and age of the patients. Although the incidence of complicated acute pancreatitis declined in both men and women between 1990 and 2004, it started to increase in both sexes (APC 3.0; 95% CI: 0.5, 5.5 in men; APC 5.4; 95% CI: 2.6, 8.2 in women) from 2005 onwards.Conclusion: Based on nationwide data, the incidence of first-time acute pancreatitis has increased in Sweden over a period of 24 years. The incidence of disease-related complications has also been on the rise during the past few years, after declining for more than 15 years before that.
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| 4. |
- Ekedahl, Anders, et al.
(författare)
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Impact of postal and telephone reminders on pick-up rates of unclaimed e-prescriptions.
- 2008
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Ingår i: Pharmacy World & Science. - : Springer Netherlands. - 0928-1231 .- 1573-739X. ; 30:5, s. 503-508
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the impact of a reminder (i.e., a mailed letter or short telephone call) from the pharmacy to patients, compared with no reminder in a control group, on the pick-up rates of unclaimed e-prescriptions. METHOD: Patients, with e-prescriptions transmitted to four large community pharmacies in two counties in northern Sweden and remaining unclaimed after 4 weekdays, were randomised to one of two intervention groups (a mailed reminder or a short telephonic reminder) or a control group. MAIN OUTCOME MEASURES: Rates of patients' pick-up of their e-prescriptions at follow-up after about 1, 2 and 3 weeks. RESULTS: Altogether, 320 patients with e-prescriptions, transmitted from March 21 through April 6 and not picked-up or dispensed, were identified and randomised to the study. There were no statistically significant differences in overall pick-up rates between the groups or with respect to gender. However, pick-up rates increased with increasing age. Higher pick-up rates were observed for two subgroups (but only in the mailed reminder group compared with controls)--for cardiovascular drugs to men and for respiratory drugs to adolescents and young adults. CONCLUSION: A reminder (i.e., a mailed letter or short telephone call) from the pharmacy to the patient had no statistically significant effect on overall pick-up rates of unclaimed e-prescriptions compared with no reminders.
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| 5. |
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| 6. |
- Khalili, Bita, et al.
(författare)
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Associations between common genetic variants and income provide insights about the socioeconomic health gradient
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EA's genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
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| 7. |
- Lundqvist, Johan, et al.
(författare)
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Innovative drinking water treatment techniques reduce the disinfection-induced oxidative stress and genotoxic activity
- 2019
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Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 5, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- Disinfection of drinking water using chlorine can lead to the formation of genotoxic by-products whenchlorine reacts with natural organic matter (NOM). A vast number of such disinfection by-products(DBPs) have been identified, making it almost impossible to routinely monitor all DBPs with chemicalanalysis. In this study, a bioanalytical approach was used, measuring oxidative stress (Nrf2 activity),genotoxicity (micronucleus test), and aryl hydrocarbon receptor (AhR) activation to evaluate an innovativewater treatment process, including suspended ion exchange, ozonation, in-line coagulation,ceramic microfiltration, and granular activated carbon. Chlorination was performed in laboratory scaleafter each step in the treatment process in order to investigate the effect of each treatment process to theformation of DBPs. Suspended ion exchange had a high capacity to remove dissolved organic carbon(DOC) and to decrease UV absorbance and Nrf2 activity in non-chlorinated water. High-dose chlorination(10 mg Cl2 L-1) of raw water caused a drastic induction of Nrf2 activity, which was decreased by 70% inwater chlorinated after suspended ion exchange. Further reduction of Nrf2 activity following chlorinationwas achieved by ozonation and the concomitant treatment steps. The ozonation treatment resulted indecreased Nrf2 activity in spite of unchanged DOC levels. However, a strong correlation was found betweenUV absorbing compounds and Nrf2 activity, demonstrating that Nrf2 inducing DBPs were formedfrom pre-cursors of a specific NOM fraction, constituted of mainly aromatic compounds. Moreover, highdosechlorination of raw water induced genotoxicity. In similarity to the DOC levels, UV absorbance andNrf2 activity, the disinfection-induced genotoxicity was also reduced by each treatment step of theinnovative water treatment technique. AhR activity was observed in the water produced by the conventionalprocess and in the raw water, but the activity was clearly decreased by the ozonation step inthe innovative water treatment process.
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| 8. |
- Jayaweera, Sanduni Wasana, et al.
(författare)
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Mechanisms of Transthyretin Inhibition of IAPP Amyloid Formation
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-formation by the islet amyloid polypeptide (IAPP), produced by the β-cells in the human pancreas, has been associated with the development of type II diabetes mellitus (T2DM). The human plasma-protein transthyretin (TTR), a well-known amyloid-inhibiting protein, is interestingly also expressed within the IAPP producing β-cells. In the present study, we have characterized the ability of TTR to interfere with IAPP amyloid-formation, both in terms of its intrinsic stability as well as with regard to the effect of TTR-stabilizing drugs. The results show that TTR can prolong the lag-phase as well as impair elongation in the course of IAPP-amyloid formation. We also show that the interfering ability correlates inversely with the thermodynamic stability of TTR, while no such correlation was observed as a function of kinetic stability. Furthermore, we demonstrate that the ability of TTR to interfere is maintained also at the low pH environment within the IAPP-containing granules of the pancreatic β-cells. However, at both neutral and low pH, the addition of TTR-stabilizing drugs partly impaired its efficacy. Taken together, these results expose mechanisms of TTR-mediated inhibition of IAPP amyloid-formation and highlights a potential therapeutic target to prevent the onset of T2DM.
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