| 1. |
- Bjerre, Mette, et al.
(författare)
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Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment : A CLARICOR trial 10-year follow-up substudy
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 301, s. 8-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Elevated circulating levels of osteoprotegerin (OPG) are known to add to the prediction of cardiovascular mortality. Our objective was to clarify the long-term risk associated with serum OPG and the possible influence of diabetes and statins on OPG levels in patients with stable coronary artery disease (CAD).METHODS: We assessed the placebo-treated group (n = 1998) from the CLARICOR trial (NCT00121550), a cohort with stable CAD. At entry, 15% of the participants had diabetes and 41% received statins. Serum OPG levels were measured in blood drawn at randomization. Participants were followed through public registers for 10 years.RESULTS: OPG levels correlated positively with diabetes status, age, CRP and female sex, but negatively with the use of statins. CAD participants with diabetes had significantly elevated serum OPG levels compared to participants without diabetes, p < 0.0001. The participants without diabetes treated with statins presented with significantly lower serum OPG levels than the corresponding non-statin-users (p < 0.0001). However, statin use showed no association with OPG levels in the participants with diabetes. High OPG levels at entry showed long-term associations with all-cause mortality and cardiovascular events (hazard ratio associated with factor 10 OPG increase 15.9 (95% CI 11.0-22.9) and 6.38 (4.60-8.90), p = 0.0001, even after adjustment for standard predictors (3.16 (1.90-5.25) and 2.29 (1.53-3.44), p < 0.0001).CONCLUSIONS: Circulating OPG holds long-term independent predictive ability for all-cause mortality and cardiovascular events in CAD participants. OPG levels were associated with diabetes, age, and female sex and statin treatment was associated with lower OPG levels in the absence of diabetes.
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| 2. |
- Bjorndal, Lars, et al.
(författare)
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Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy
- 2010
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Ingår i: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 118:3, s. 290-297
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Tidskriftsartikel (refereegranskat)abstract
- Less invasive excavation methods have been suggested for deep caries lesions. We tested the effects of stepwise vs. direct complete excavation, 1 yr after the procedure had been carried out, in 314 adults (from six centres) who had received treatment of a tooth with deep caries. The teeth had caries lesions involving 75% or more of the dentin and were centrally randomized to stepwise or direct complete excavation. Stepwise excavation resulted in fewer pulp exposures compared with direct complete excavation [difference: 11.4%, 95% confidence interval (CI) (1.2; 21.3)]. At 1 yr of follow-up, there was a statistically significantly higher success rate with stepwise excavation, with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [difference: 11.7%, 95% CI (0.5; 22.5)]. In a subsequent nested trial, 58 patients with exposed pulps were randomized to direct capping or partial pulpotomy. We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [31.8% and 34.5%; difference: 2.7%, 95% CI (−22.7; 26.6)]. In conclusion, stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation. In view of the poor prognosis of vital pulp treatment, a stepwise excavation approach for managing deep caries lesions is recommended.
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| 3. |
- Bjørkskov, Frederik Bühring, et al.
(författare)
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Purification and functional comparison of nine human Aquaporins produced in Saccharomyces cerevisiae for the purpose of biophysical characterization
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The sparse number of high-resolution human membrane protein structures severely restricts our comprehension of molecular physiology and ability to exploit rational drug design. In the search for a standardized, cheap and easily handled human membrane protein production platform, we thoroughly investigated the capacity of S. cerevisiae to deliver high yields of prime quality human AQPs, focusing on poorly characterized members including some previously shown to be difficult to isolate. Exploiting GFP labeled forms we comprehensively optimized production and purification procedures resulting in satisfactory yields of all nine AQP targets. We applied the obtained knowledge to successfully upscale purification of histidine tagged human AQP10 produced in large bioreactors. Glycosylation analysis revealed that AQP7 and 12 were O-glycosylated, AQP10 was N-glycosylated while the other AQPs were not glycosylated. We furthermore performed functional characterization and found that AQP 2, 6 and 8 allowed flux of water whereas AQP3, 7, 9, 10, 11 and 12 also facilitated a glycerol flux. In conclusion, our S. cerevisiae platform emerges as a powerful tool for isolation of functional, difficult-To-express human membrane proteins suitable for biophysical characterization.
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| 4. |
- Blicharska, Malgorzata, 1979-, et al.
(författare)
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Between biodiversity conservation and sustainable forest management - A multidisciplinary assessment of the emblematic Bialowieza Forest case
- 2020
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- The tension between biodiversity conservation and multipurpose forest management may lead to conflicts. An internationally prominent example is the Bialowieza Forest Massif (BFM), an extensive forest complex with high levels of naturalness. We apply a systematic, multidisciplinary assessment process to review empirical evidence on different dimensions of the BFM conflict. While there is broad consensus that this forest massif is an exceptional place worth conserving and that a way forward is a zonation system combining conservation with management, exactly how this should be done has yet to be agreed upon. Our assessment shows that the key reasons for the BFM controversy go beyond the availability of knowledge on the ecological status of the BFM and include: 1) evidence stemming from different sources, which is often contradictory and prone to different interpretations; 2) knowledge gaps, particularly with regard to socio-economic drivers and beneficiaries as well as uncertainties about future trends; 3) fundamentally different values and priorities among stakeholder groups, resulting in power struggles, and an overall lack of trust. We conclude that evidence-based knowledge alone is insufficient to cope with complex conservation conflicts. While more evidence may help assess the consequences of decisions, the actual management decisions depend on different actors' worldviews, which are rooted in their professional identities and power, and their political and legal realities. This calls for conflict management through a well-organized participatory process organized and supervised by a body deemed legitimate by the groups involved.
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| 5. |
- Carlsson, Axel C, et al.
(författare)
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10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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| 6. |
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| 7. |
- Cronberg, Tobias, et al.
(författare)
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Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33 degrees C vs 36 degrees C After Out-of-Hospital Cardiac Arrest A Randomized Clinical Trial
- 2015
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 72:6, s. 634-641
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. OBJECTIVE To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. INTERVENTIONS Targeted temperature management at 33 degrees C vs 36 degrees C. MAIN OUTCOMES AND MEASURES Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS In the modified intent-to-treat population, including nonsurvivors, the median MMSE score was 14 in the 33 degrees C group (interquartile range [IQR], 0-28) vs 17 in the 36 degrees C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR, 79-130) vs 115 (IQR, 80-130) (P = .57) in the 33 degrees C and 36 degrees C groups, respectively. The median MMSE score for survivors was within the reference range and similar (33 degrees C group median, 28; IQR, 26-30; vs 36 degrees C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was within the minor deficit range (33 degrees C group median, 79.5; IQR, 78.0-85.9; vs 36 degrees C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs 17.5% of survivors reported needing help with everyday activities (P = .71), and 66.5% in the 33 degrees C group vs 61.8% in the 36 degrees C group reported that they thought they had made a complete mental recovery (P = .32). The mean (SD) mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P = .45), comparable to the population norm. CONCLUSIONS AND RELEVANCE Quality of life was good and similar in patients with cardiac arrest receiving targeted temperature management at 33 degrees C or 36 degrees C. Cognitive function was similar in both intervention groups, but many patients and observers reported impairment not detected previously by standard outcome scales.
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| 8. |
- Gotfryd, Kamil, et al.
(författare)
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Human adipose glycerol flux is regulated by a pH gate in AQP10
- 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
- Obesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation-an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications.
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| 9. |
- Hyttel-Sorensen, Simon, et al.
(författare)
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A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC) : study protocol for a randomized controlled trial
- 2013
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14, s. 120-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Every year in Europe about 25,000 infants are born extremely preterm. These infants have a 20% mortality rate, and 25% of survivors have severe long-term cerebral impairment. Preventative measures are key to reduce mortality and morbidity in an extremely preterm population. The primary objective of the SafeBoosC phase II trial is to examine if it is possible to stabilize the cerebral oxygenation of extremely preterm infants during the first 72 hours of life through the application of cerebral near-infrared spectroscopy (NIRS) oximetry and implementation of an clinical treatment guideline based on intervention thresholds of cerebral regional tissue saturation rStO(2). Methods/Design: SafeBoosC is a randomized, blinded, multinational, phase II clinical trial. The inclusion criteria are: neonates born more than 12 weeks preterm; decision to conduct full life support; parental informed consent; and possibility to place the cerebral NIRS oximeter within 3 hours after birth. The infants will be randomized into one of two groups. Both groups will have a cerebral oximeter monitoring device placed within three hours of birth. In the experimental group, the cerebral oxygenation reading will supplement the standard treatment using a predefined treatment guideline. In the control group, the cerebral oxygenation reading will not be visible and the infant will be treated according to the local standards. The primary outcome is the multiplication of the duration and magnitude of rStO(2) values outside the target ranges of 55% to 85%, that is, the 'burden of hypoxia and hyperoxia' expressed in '%hours'. To detect a 50% difference between the experimental and control group in %hours, 166 infants in total must be randomized. Secondary outcomes are mortality at term date, cerebral ultrasound score, and interburst intervals on an amplitude-integrated electroencephalogram at 64 hours of life and explorative outcomes include neurodevelopmental outcome at 2 years corrected age, magnetic resonance imaging at term, blood biomarkers at 6 and 64 hours after birth, and adverse events. Discussion: Cerebral oximetry guided interventions have the potential to improve neurodevelopmental outcome in extremely preterm infants. It is a logical first step to test if it is possible to reduce the burden of hypoxia and hyperoxia.
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| 10. |
- Højskov, Ida Elisabeth, et al.
(författare)
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Early physical and psycho-educational rehabilitation in patients with coronary artery bypass grafting: A randomized controlled trial.
- 2019
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 51:2, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- Rehabilitation of patients following coronary artery bypass grafting (CABG) has been widely studied; however, research into early rehabilitation after CABG is sparse. The aim of this trial was to assess the impact of early rehabilitation, compared with usual care in patients following CABG.Randomized controlled trial.A total of 326 patients treated with CABG.Patients treated with CABG were randomized 1:1 to 4 weeks of comprehensive early rehabilitation or usual care. The primary outcome was the Six Minute Walk Test (6MWT). Secondary outcomes were mental health and physical activity (Medical Outcome Study Short Form; SF-12); anxiety and depression (Hospital Anxiety and Depression Scale; HADS); physical and emotional scores; sleep (Pittsburgh Sleep Quality Index; PSQI); pain (Örebro Musculoskeletal Screening Questionnaire; ÖMSQ) and muscle endurance (Sit-To-Stand test).Sixteen patients dropped out. No significant differences between groups in the primary outcome (6MWT) were found after 4 weeks (p = 0.27). For secondary outcomes the odds ratio of HADS-D ≥ 8 decreased in favour of the experimental intervention (p = 0.04). There was non-adherence to parts of the intervention. Per-protocol analysis showed differences between groups for the 6MWT (p = 0.02) and the Sit-To-Stand test (p = 0.046).In general, the intervention had no effect on the 6MWT, or secondary outcomes, except for depressive symptoms. However, in adherent participants, the intervention had a positive effect for the primary and several secondary outcomes.
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