1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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3. |
- Welen, Karin, et al.
(author)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
-
In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Journal article (peer-reviewed)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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4. |
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5. |
- Eldén, Sara, et al.
(author)
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Introduktion: Välkommen till efterfesten!
- 2014
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In: Efter festen: Om konsten att utvecklas från doktor till docent. - 9789144094809 ; , s. 21-36
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Book chapter (other academic/artistic)
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6. |
- Hallonsten, Olof, et al.
(author)
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Afterword
- 2024
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In: Metaphors We Supervise By. - 9789144184197 ; , s. 135-138
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Book chapter (other academic/artistic)
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7. |
- Hallonsten, Olof, et al.
(author)
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Introduction
- 2024
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In: Metaphors We Supervise By. - 9789144184197 ; , s. 7-12
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Book chapter (other academic/artistic)
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8. |
- Hesselman, Susanne, 1973-, et al.
(author)
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Time matters—a Swedish cohort study of labor duration and risk of uterine rupture
- 2021
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In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:10, s. 1902-1909
-
Journal article (peer-reviewed)abstract
- IntroductionUterine rupture is an obstetric emergency associated with maternal and neonatal morbidity. The main risk factor is a prior cesarean section, with rupture occurring in subsequent labor. The aim of this study was to assess the risk of uterine rupture by labor duration and labor management.Material and methodsThis is a Swedish register-based cohort study of women who underwent labor in 2013–2018 after a primary cesarean section (n = 20 046). Duration of labor was the main exposure, calculated from onset of regular labor contractions and birth; both timepoints were retrieved from electronic medical records for 12 583 labors, 63% of the study population. Uterine rupture was calculated as events per 1000 births at different timepoints during labor. Risk estimates for uterine rupture by labor duration, induction of labor, use of oxytocin and epidural analgesia were calculated using Poisson regression, adjusted for maternal and birth characteristics. Estimates were presented as adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe prevalence of uterine rupture was 1.4% (282/20 046 deliveries). Labor duration was 9.88 hours (95% CI 8.93–10.83) for women with uterine rupture, 8.20 hours (95% CI 8.10–8.31) for women with vaginal delivery, and 10.71 hours (95% CI 10.46–10.97) for women with cesarean section without uterine rupture. Few women (1.0/1000) experienced uterine rupture during the first 3 hours of labor. Uterine rupture occurred in 15.6/1000 births with labor duration over 12 hours. The highest risk for uterine rupture per hour compared with vaginal delivery was observed at 6 hours (ARR 1.20, 95% CI 1.11–1.30). Induction of labor was associated with uterine rupture (ARR 1.54, 95% CI 1.19–1.99), with a particular high risk seen in those induced with prostaglandins and no risk observed with cervical catheter (ARR 1.19, 95% CI 0.83–1.71). Labor augmentation with oxytocin (ARR 1.60, 95% CI 1.25–2.05) and epidural analgesia (ARR 1.63, 95% CI 1.27–2.10) were also associated with uterine rupture.ConclusionsLabor duration is an independent factor for uterine rupture among women attempting vaginal delivery after cesarean section. Medical induction and augmentation of labor increase the risk, regardless of maternal and birth characteristics.
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9. |
- Jonsson, Anna, et al.
(author)
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Detective work
- 2024
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In: Metaphors We Supervise By. - 9789144184197 ; , s. 47-52
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Book chapter (other academic/artistic)
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10. |
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11. |
- Rosengren, Anders, et al.
(author)
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Reduced Insulin Exocytosis in Human Pancreatic β-cells With Gene Variants Linked to Type 2 Diabetes.
- 2012
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 61:7, s. 1726-1733
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Journal article (peer-reviewed)abstract
- The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation to genetic risk profiles in diabetic and nondiabetic donors. Islets from donors with T2D exhibited impaired insulin secretion, which was more pronounced in lean than obese diabetic donors. We assessed the impact of 14 disease susceptibility variants on measures of glucose sensing, exocytosis, and structure. Variants near TCF7L2 and ADRA2A were associated with reduced glucose-induced insulin secretion, whereas susceptibility variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoked insulin exocytosis. KCNQ1, ADRA2A, KCNJ11, HHEX/IDE, and SLC2A2 variants affected granule docking. We combined our results to create a novel genetic risk score for β-cell dysfunction that includes aberrant granule docking, decreased Ca(2+) sensitivity of exocytosis, and reduced insulin release. Individuals with a high risk score displayed an impaired response to intravenous glucose and deteriorating insulin secretion over time. Our results underscore the importance of defects in β-cell exocytosis in T2D and demonstrate the potential of cellular phenotypic characterization in the elucidation of complex genetic disorders.
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12. |
- Skogh, Anna, et al.
(author)
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An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice
- 2018
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In: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 28:14, s. 2446-2450
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Journal article (peer-reviewed)abstract
- The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1-7 (SP1-7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1-7 and the tetrapeptide endomorphin-2 that is also binding to the SP1-7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50) of 4 was superior as compared to gabapentin and morphine that are used in clinic.
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13. |
- Welén, Karin, 1970, et al.
(author)
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A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
-
In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
-
Journal article (peer-reviewed)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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14. |
- Ahlbeck Bergendahl, Ida, et al.
(author)
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Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
- 2016
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Reports (other academic/artistic)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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15. |
- Ahlqvist, Emma, et al.
(author)
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A link between GIP and osteopontin in adipose tissue and insulin resistance.
- 2013
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2088-2094
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Journal article (peer-reviewed)abstract
- Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.
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16. |
- Alkmark, Mårten, et al.
(author)
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Efficacy and safety of oral misoprostol vs transvaginal balloon catheter for labor induction : An observational study within the SWEdish Postterm Induction Study (SWEPIS)
- 2021
-
In: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Induction of labor is increasing in the world. A common indication for Induction of labor is late term and postterm pregnancy at 41 gestational week and thereafter. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0-1 gestational weeks.MATERIAL AND METHODS: In this observational study, based on data from Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1 213 women with a low-risk singleton pregnancy at 41 to 42 gestational weeks were induced with oral misoprostol (n=744) or transvaginal balloon catheter (n=469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 hours and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time-to-vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analogue scale. We present crude and adjusted mean differences and relative risks (RR) with 95% confidence interval (CI). Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score.RESULTS: Vaginal delivery within 24 hours was significantly lower in the misoprostol compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 [95% CI 0.64; 0.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31; 1.89]; maternal composite (2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58; 4.97]). Adjusted mean time-to-vaginal delivery was increased by 3.8 hours (95% CI 1.3; 6.2) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups.CONCLUSION: Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 hours and a longer time-to-vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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17. |
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18. |
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19. |
- Andersson, Lotta, et al.
(author)
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Underlag till kontrollstation 2015 för anpassning till ett förändrat klimat
- 2015
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Reports (other academic/artistic)abstract
- När klimatet förändras påverkas människor och deras egendom, företag, kommunal och statlig verksamhet, vilket gör att såväl myndigheter, kommuner, företag som enskilda fastighetsägare måste agera.Översvämningar, värmeböljor, ras och skred är bara några exempel på vad vi behöver rusta oss för. Vi ska möta klimatförändringar som sker här i Sverige, men vi måste också anpassa oss till vad klimatförändringar i andra länder innebär för Sverige.Kostnaderna för klimatanpassning kan bli höga, men bedöms av bland andra EUkommissionen ändå löna sig i förhållande till de skadekostnader som uppstår om inga åtgärder vidtas.Klimatanpassningsarbetet i Sverige har gått framåt under de senaste åren. Några exempel på myndighetsuppdrag är Nationell höjddatabas, Ras- och skredkarteringen av Göta älvdalen, Dricksvattenutredningen, länsstyrelsernas regionala handlingsplaner för klimatanpassning, samt inrättandet av Nationellt kunskapscentrum för klimatanpassning.Sveriges meteorologiska och hydrologiska instituts arbete med regeringsuppdraget att utarbeta underlag till kontrollstation 2015 för anpassning till ett förändrat klimat, visar på stort behov av fortsatta insatser. Denna rapport ger förslag till en färdplan för klimatanpassningen i Sverige. Slutsatserna handlar framförallt om att arbetet måste bedrivas långsiktigt, att roller och mandat förtydligas samt att en bättre samordning mellan olika aktörer uppnås.De viktigaste slutsatserna för fortsatt arbete är:Regelverk behöver anpassas, roller och ansvar samt strategier och mål måstetydliggörasPrioriterade forsknings- och utvecklingsinsatser, som fyller identifierade kunskapsbehov inklusive långtidsövervakning, behöver finansierasKunskap, beslutstöd och prognos- och varningssystem behöver göras mer tillgängligaHur kostnader ska fördelas mellan olika aktörer och hur resurser till prioriterade åtgärder ska säkerställas, behöver klarläggasUppdraget har inneburit att sammanställa kunskap om nuvarande och framtida risker och konsekvenser för samhället av ett förändrat klimat, till exempel effekter på samhällsviktiga funktioner och människors hälsa. Arbetet har också omfattat en kartläggning över vad som genomförts sedan Klimat- och sårbarhetsutredningen presenterades år 2007. Utifrån det underlaget har målet varit att beskriva behoven och lämna förslag på åtgärder för anpassning av olika delar av samhället. Hänsyn har tagits till EU:s strategi för klimatanpassning. Arbetet har bedrivits i bred samverkan med myndigheter, kommuner, forskare, branschorganisationer och andra näringslivsrepresentanter.Redovisningen av uppdraget omfattar en huvudrapport samt 18 bilagor. Huvudrapportens tredje kapitel är en syntes av rapportens alla förslag, och kan ses som färdplanen för att säkerställa att Sverige klimatanpassas.
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20. |
- Axelsson, Mette, et al.
(author)
-
Mat vid diabetes. : En systematisk översikt med utvärdering av effekter samt hälsoekonomiska och etiska aspekter.
- 2022
-
Reports (other academic/artistic)abstract
- SlutsatserTyp 1- och typ 2-diabetes Det finns ett samband mellan att äta medelhavskost och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det finns ett samband mellan att äta en större andel2 fibrer eller baljväxter och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel nötter och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet) samt lägre risk att insjukna i hjärt- och kärlsjukdom (låg tillförlitlighet). Det finns ett samband mellan att dricka mer2 kaffe och lägre risk att dö i förtid oavsett orsak och lägre risk att dö i förtid i kranskärlssjukdom (måttlig tillförlitlighet) samt möjligen en lägre risk att dö i förtid i hjärt- och kärlsjukdom (låg tillförlitlighet). Det råder generell brist på studier med lång uppföljningstid som jämför inverkan av olika slags kostråd på överlevnad, diabeteskomplikationer, diabetesremission3, livskvalitet och biverkningar. Tillförlitligheten av befintliga resultat är dessutom mycket låg för de flesta koster, kostbehandlingar, livsmedel och näringsämnen som har utvärderats. Effekter på hälsa och relaterade mått kan i dessa fall inte bedömas.2. Begreppet ”större andel” eller ”mer” avser inte nödvändigtvis att äta eller dricka mer totalt utan att öka mängden av ett visst livsmedel genom att byta ut annan mat eller dryck.Typ 2-diabetes Det kan finnas ett samband mellan att äta en större andel mättat fett och högre risk för att dö i förtid av hjärt- och kärlsjukdom (låg tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel enkelomättat fett och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet). En behandling med en initial period av kraftigt minskat energiintag med hjälp av lågenergipulver (VLED) med efterföljande övergång till mat för viktstabilitet jämfört med vanlig kostbehandling har gynnsamma effekter på livskvalitet (enligt EQ-5D), långtidsblodsocker (HbA1c) och vikt upp till 12 månader (måttlig tillförlitlighet)4. Vidare kan metoder där VLED ingår ha gynnsamma effekter på diabetesremission5 och midjeomfång upp till 12 månader (låg tillförlitlighet) och långtidsblodsocker (HbA1c) upp till 24 månader (låg tillförlitlighet). Intensiv livsstilsbehandling därlågfettkost kombineras med fysisk aktivitet och minskat energiintag har gynnsamma effekter jämfört med vanlig kostbehandling på långtidsblodsocker (HbA1c), vikt, kroppsmasseindex (BMI), midjeomfång och vissa blodfetter upp till 12 månader (måttlig tillförlitlighet)3. Viktminskningen kan kvarstå upp till omkring 10 år (låg tillförlitlighet). Behandlingen kan leda till bättre fysisk livskvalitet upp till 8 år (låg tillförlitlighet) medan effektskillnaden i psykisk livskvalitet under samma tid kan vara obefintlig eller försumbar (låg tillförlitlighet). Jämförelsen påvisar ingen förändrad risk att dö i förtid oavsett orsak eller att dö eller insjukna av kardiovaskulära orsaker efter omkring 10 år (låg tillförlitlighet). I det hälsoekonomiska perspektivet är intensiv livsstilsbehandling mer resurskrävande än vanlig kostbehandling, och beräkningar visar små eller inga vinster i kvalitetsjusterade levnadsår (QALYs) på individnivå. Energirestriktion i samband med intensiv livsstilsbehandling med ketogen kost eller med högproteinkost (20 E%) i kombination med fysisk aktivitet jämfört med vanlig kostbehandling kan ge en viktminskning upp till 11 månader (låg tillförlitlighet) men det saknas studier som kan visa om vikten kan bibehållas på längre sikt. Det saknas studier som undersökt kliniskt viktiga utfall som dödlighet, kardiovaskulära sjukdomar, livskvalitet och diabetesremission.3. Gäller endast vid typ 2-diabetes.4. Utgår från individer med en medelkroppsvikt på cirka 100 kg och medel-HbA1c på 60 mmol/mol.5. Resultaten för utfallet diabetesremission (att uppnå normala blodsockervärden) gäller när en diabetesdiagnos sattes för mindre än 6 år sedan eller för mindre än 3 år sedan. Definitionen för diabetesremission var ett HbA1c på mindre än 48 mmol/mol och att samtidigt vara fri från blodsockersänkande läkemedel.Graviditetsdiabetes Det saknas studier om kost vid graviditetsdiabetes med tillräcklig tillförlitlighet för att kunna bedöma effekterna.
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21. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
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Strategies to improve usability and preserve accuracy in biological sequence databases
- 2016
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 16:18, s. 2454-2460
-
Journal article (peer-reviewed)abstract
- Biology is increasingly dependent on large-scale analysis, such as proteomics, creating a requirement for efficient bioinformatics. Bioinformatic predictions of biological functions rely upon correctly annotated database sequences, and the presence of inaccurately annotated or otherwise poorly described sequences introduces noise and bias to biological analyses. Accurate annotations are, for example, pivotal for correct identifications of polypeptide fragments. However, standards for how sequence databases are organized and presented are currently insufficient. Here, we propose five strategies to address fundamental issues in the annotation of sequence databases: (i) to clearly separate experimentally verified and unverified sequence entries; (ii) to enable a system for tracing the origins of annotations; (iii) to separate entries with high-quality, informative annotation from less useful ones; (iv) to integrate automated quality-control software whenever such tools exist; and (v) to facilitate post-submission editing of annotations and metadata associated with sequences. We believe that implementation of these strategies, for example as requirements for publication of database papers, would enable biology to better take advantage of large-scale data.
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22. |
- Berglund, Lisa, et al.
(author)
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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
- 2016
-
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
-
Journal article (peer-reviewed)abstract
- Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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23. |
- Bexelius, Maria, et al.
(author)
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27 forskare : Så kan EU:s murar rivas
- 2015
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In: Dagens samhälle. - : Sveriges kommuner och landsting. - 1652-6511. ; :20150923
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Journal article (pop. science, debate, etc.)
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24. |
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25. |
- Blondal, Anna Bryndis, et al.
(author)
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General practitioners' perceptions of the current status and pharmacists' contribution to primary care in Iceland.
- 2017
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In: International Journal of Clinical Pharmacy. - : Springer Science and Business Media LLC. - 2210-7703 .- 2210-7711. ; 39:4, s. 945-952
-
Journal article (peer-reviewed)abstract
- Background For the past several years pharmacists' responsibilities have expanded globally from traditional tasks of dispensing medications to collaborating with other health care professionals in patient care. Similar developments have not occurred in outpatient settings in Iceland. Objective The aim of this study was to explore Icelandic general practitioners' views on the current status of primary care, their perceptions of pharmacists as a health care profession, and their attitudes towards future GP-pharmacist collaboration in primary care in Iceland. Setting Twelve primary care clinics in Iceland. Methods Semi-structured in-depth interviews were conducted with general practitioners from different primary care clinics in Iceland. A purposive and snowball sampling technique was used to select participants. All interviews were recorded and transcribed verbatim. The transcripts were categorized by themes and then analyzed using conventional content analysis. Main outcome measure General practitioners' attitudes towards pharmacists. Results Twenty general practitioners from twelve different primary care clinics in Iceland were interviewed. There are several unmet needs regarding medicines and patient monitoring in the Icelandic health care system. General practitioners suggested ways in which these gaps may be addressed and pharmacist-led clinical service was one of the suggestions. Currently, their communication with pharmacists in the primary sector solely surrounds practical non-clinical issues. Due to increasing polypharmacy and multimorbidity, they suggested that pharmacists should be more involved in patient care. Conclusions General practitioners believe that pharmacist-led clinical service can increase the quality of patient therapy. To improve communication between these health care providers, pharmacists must also re-professionalize (strengthening the profession´s status through new responsibilities and tasks), not having a conflict of interest and showing that they have expertise in patient care.
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26. |
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27. |
- Causevic, Sara, et al.
(author)
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Prevalence and risk factors for transactional sex among Swedish-born and foreign-born MSM in Sweden
- 2022
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In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 22
-
Journal article (peer-reviewed)abstract
- Background: Little is known about transactional sex (TS) (selling and buying sex) among men who have sex with men (MSM) in Sweden, especially among foreign-born MSM. This study aims to assess the prevalence and risk factors of TS (ever and in the previous five years) among MSM living in Sweden and to determine if there is a difference between Swedish-born MSM and foreign-born MSM.Methods: Swedish data from a multicountry online banner survey (EMIS-2017) was used (n = 4443). Multivariable regression analysis was applied to analyse the data.Results: The prevalence of ever-selling sex among all MSM participants was 13.2% and 5.9% in the previous five years. Selling sex ever and in the previous five years was higher among foreign-born MSM (16% and 8.4%, respectively) than Swedish-born MSM (12.7% and 5.4%, respectively). Among all participants, younger age (aOR:3.19, 95% CI:1.57-6.45) and really struggling to live on current income (aOR:3.37, 95% CI:2.29-4.96) increased the odds of selling sex. Being foreign-born MSM (aOR:1.33, 95% CI:1.02-1.73) and having had sex with a woman in the previous 12 months increased the odds of selling sex (aOR:1.44, 95% CI:1.00-2.07). The prevalence of ever buying sex among MSM participants in Sweden was 10.8% and 6.7% in the previous five years, with the same trend among foreign-born MSM (11.6% and 6.9%, respectively) and Swedish-born MSM (10.7% and 6.6%, respectively). Higher education and not having a current partner increased the odds of buying sex. Younger age was protective for buying sex (aOR:0.05, 95% CI:0.02-0.14). Among the foreign-born MSM, the length of stay in Sweden decreased the odds of buying sex (aOR: 0.98, 95% CI: 0.96-0.99).Conclusions: The comparatively high prevalence of TS among MSM participants in Sweden, where buying sex is illegal, with a higher prevalence among foreign-born MSM participants, calls for sexual and reproductive health and rights interventions in this population. Increased attention, including HIV prevention programming and education, should be aimed at younger MSM, MSM struggling with their current income, and foreign-born MSM, as they are more likely to report selling sex.
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28. |
- Dahlgren, Markus, et al.
(author)
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Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
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Journal article (peer-reviewed)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
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29. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
-
In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
-
Journal article (peer-reviewed)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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30. |
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31. |
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32. |
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33. |
- Eriksson, Susanne, et al.
(author)
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Different beef breed sires used for crossbreeding with Swedish dairy cows - effects on calving performance and carcass traits
- 2020
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In: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 232
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Journal article (peer-reviewed)abstract
- Improved potential for weight gain and carcass classification traits in calves aimed at slaughter from dairy herds would increase the calves' economic value, and enable an increased beef production. At present, relatively low economic weights are placed on beef traits in the comprehensive Nordic dairy cattle breeding goal. An effective way to improve beef production from dairy herds is therefore to inseminate a larger proportion of dairy heifers and cows with beef bull semen. In the choice of beef bull breed, both effects on calving traits, carcass weight gain and carcass traits need to be considered. The aim of this study was therefore to compare different beef x dairy crosses regarding calving performance and carcass traits. Field data comprising in total close to 1.6 million calving records from Swedish herds, and more than 1.1 million carcass records from commercial slaughter houses, were analyzed using linear models. Differences in least-square means between different breed combinations were estimated for percentage of calving difficulty, stillbirth, daily carcass gain, carcass weight, EUROP conformation and fat classification. The dams were purebred Swedish Red (SR) or Swedish Holstein (SH), and the sires were either of purebred dairy (SR or SH) or of the beef breeds Angus, Hereford, Limousin, Simmental or Charolais. The results showed that crossbreeding dairy cows with beef bulls, especially of late maturing breeds, has potential to considerably improve beef production from dairy herds. Improvement of carcass characteristics and carcass gain were most noticeable in young crossbred bulls, where the highest increase for single breed combinations was 67% for conformation and 17% for carcass gain. Offspring of different beef x dairy combinations displayed varying average carcass gain and characteristics in terms of fatness and conformation in heifers, steers and young bulls, and would fit different types of production systems. Whereas crossbreeding had small or favorable effects on stillbirth, the use of late maturing beef breed sires negatively influenced the calving performance, especially in primiparous dairy cows. By choosing individual beef bulls with high estimated breeding values for calving ease, the percentage of calving difficulty could be reduced, even when using late maturing beef breed sires for crossbreeding.
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34. |
- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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35. |
- Glimelius, Bengt, et al.
(author)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
-
Journal article (peer-reviewed)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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36. |
- Grande, Giulia, et al.
(author)
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Disability trajectories and mortality in older adults with different cognitive and physical profiles
- 2020
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In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:6, s. 1007-1016
-
Journal article (peer-reviewed)abstract
- Background Cognitive and physical deficits independently raise the risk for negative events in older adults. Less is known about whether their co-occurrence constitutes a distinct risk profile. This study quantifies the association between cognitive impairment, no dementia (CIND), slow walking speed (WS) and their combination and disability and mortality.Methods We examined 2546 dementia-free people aged >= 60 years, part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) up to 12 years. The following four profiles were created: (1) healthy profile; (2) isolated CIND (scoring 1.5 SD below age-specific means on at least one cognitive domain); (3) isolated slow WS (< 0.8 m/s); (4) CIND+ slow WS. Disability was defined as the sum of impaired activities of daily living and trajectories of disability were derived from mixed-effect linear regression models. Piecewise proportional hazard models were used to estimate mortality rate [hazard ratios (HRs)]. Population attributable risks of death were calculated.Results Participants with both CIND and slow WS had the worst prognosis, especially in the short-term period. They experienced the steepest increase in disability and five times the mortality rate (HR 5.1; 95% CI 3.5-7.4) of participants free from these conditions. Similar but attenuated results were observed for longer follow-ups. Co-occurring CIND and slow WS accounted for 30% of short-term deaths.Conclusions Co-occurring cognitive and physical limitations constitute a distinct risk profile in older people, and account for a large proportion of short-term deaths. Assessing cognitive and physical function could enable early identification of people at high risk for adverse events.
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37. |
- Granfors, Michaela, et al.
(author)
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Placental location and pregnancy outcomes in nulliparous women : A population-based cohort study
- 2019
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In: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 98:8, s. 988-996
-
Journal article (peer-reviewed)abstract
- Introduction: The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes.Material and methods: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes.Results: Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (<32 weeks of gestation) (adjusted OR [aOR] 1.78, 95% CI 1.18-2.63 and aOR 2.12, 95% CI 1.39-2.25, respectively), moderate preterm birth (32-36 weeks of gestation) (aOR 1.23, 95% CI 1.001-1.51 and aOR 1.62, 95% CI 1.32-2.00, respectively), small-for-gestational-age birth (aOR 1.67, 95% CI 1.34-2.07 and aOR 1.77, 95% CI 1.39-2.25, respectively) and manual removal of the placenta in vaginal births (aOR 3.27, 95% CI 2.68-3.99 and aOR 3.27, 95% CI 2.60-4.10, respectively). Additionally, lateral placental location was associated with preeclampsia (aOR 1.30, 95% CI 1.03-1.65) and severe postpartum hemorrhage (aOR 1.42, 95% CI 1.27-1.82).Conclusions: Compared with posterior placental location, fundal and lateral placental locations are associated with a number of adverse pregnancy, delivery and infant outcomes.
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38. |
- Grut, Viktor, et al.
(author)
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Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
- 2021
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In: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
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39. |
- Jonsson, Anna, et al.
(author)
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Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure
- 2020
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In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 7:3, s. 1150-1160
-
Journal article (peer-reviewed)abstract
- Aims: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate.Methods and results: One hundred forty-six HF patients (mean age 68 +/- 13 years, mean left ventricular ejection fraction 45% +/- 15) within a single-centre hospital that underwent Cr-51-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmo, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m(2). Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmo (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD.Conclusions: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.
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40. |
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41. |
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42. |
- Jonsson, Anna-Li, et al.
(author)
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Hanöbukten 2015
- 2016
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In: Faktablad: resultat från övervakningen av kustfisk.
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Other publication (pop. science, debate, etc.)
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43. |
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44. |
- Jonsson, Anna, 1981-, et al.
(author)
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Small constrained SP1-7 analogues bind to a unique site and promote anti-allodynic effects following systemic injection in mice
- 2015
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In: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 298, s. 112-119
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Journal article (peer-reviewed)abstract
- Previous results have shown that the substance P (SP) N-terminal fragment SP1–7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1–7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1–7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1–7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.
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45. |
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46. |
- Jonsson Cornell, Anna, 1973-, et al.
(author)
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Forska för en bättre värld
- 2018
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In: Upsala nya tidning. - Uppsala. - 1104-0173.
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Journal article (pop. science, debate, etc.)
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47. |
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48. |
- Jonsson, Per R., 1957, et al.
(author)
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The Barnacle Balanus improvisus as a Marine Model - Culturing and Gene Expression
- 2018
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In: Jove-Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :138
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Journal article (peer-reviewed)abstract
- Barnacles are marine crustaceans with a sessile adult and free-swimming, planktonic larvae. The barnacle Balanus (Amphibalanus) improvisus is particularly relevant as a model for the studies of osmoregulatory mechanisms because of its extreme tolerance to low salinity. It is also widely used as a model of settling biology, in particular in relation to antifouling research. However, natural seasonal spawning yields an unpredictable supply of cyprid larvae for studies. A protocol for the all-year-round culturing of B. improvisus has been developed and a detailed description of all steps in the production line is outlined (i.e., the establishment of adult cultures on panels, the collection and rearing of barnacle larvae, and the administration of feed for adults and larvae). The description also provides guidance on troubleshooting and discusses critical parameters (e.g., the removal of contamination, the production of high-quality feed, the manpower needed, and the importance of high-quality seawater). Each batch from the culturing system maximally yields roughly 12,000 nauplii and can deliver four batches in a week, so up to almost 50,000 larvae per week can be produced. The method used to culture B. improvisus is, probably, to a large extent also applicable to other marine invertebrates with free-swimming-larvae. Protocols are presented for the dissection of various tissues from adults as well as the production of high-quality RNA for studies on gene expression. It is also described how cultured adults and reared cyprids can be utilized in a wide array of experimental designs for examining gene expression in relation to external factors. The use of cultured barnacles in gene expression is illustrated with studies of possible osmoregulatory roles of Na+/K+ ATPase and aquaporins.
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49. |
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50. |
- Kauppi, Anna M., 1971-, et al.
(author)
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Inhibitors of type III secretion in Yersinia : design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
- 2007
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In: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd. - 0968-0896 .- 1464-3391. ; 15:22, s. 6994-7011
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Journal article (other academic/artistic)abstract
- Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal.
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