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| 2. |
- Bergman, Lina, et al.
(författare)
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Investigating Maternal Brain Alterations in Preeclampsia : the Need for a Multidisciplinary Effort
- 2019
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Ingår i: Current Hypertension Reports. - : Springer Science and Business Media LLC. - 1522-6417 .- 1534-3111. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia.RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.
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| 3. |
- Bergman, Lina, et al.
(författare)
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Preeclampsia and Increased Permeability Over the Blood–Brain Barrier : A Role of Vascular Endothelial Growth Receptor 2
- 2021
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.CONCLUSION: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
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| 4. |
- Bergström, Ulf, et al.
(författare)
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Long-term effects of no-take zones in Swedish waters
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Marine protected areas (MPAs) are increasingly established worldwide to protect and restore degraded ecosystems. However, the level of protection varies among MPAs and has been found to affect the outcome of the closure. In no-take zones (NTZs), no fishing or extraction of marine organisms is allowed. The EU Commission recently committed to protect 30% of European waters by 2030 through the updated Biodiversity Strategy. Importantly, one third of these 30% should be of strict protection. Exactly what is meant by strict protection is not entirely clear, but fishing would likely have to be fully or largely prohibited in these areas. This new target for strictly protected areas highlights the need to evaluate the ecological effects of NTZs, particularly in regions like northern Europe where such evaluations are scarce. The Swedish NTZs made up approximately two thirds of the total areal extent of NTZs in Europe a decade ago. Given that these areas have been closed for at least 10 years and can provide insights into long-term effects of NTZs on fish and ecosystems, they are of broad interest in light of the new 10% strict protection by 2030 commitment by EU member states.In total, eight NTZs in Swedish coastal and offshore waters were evaluated in the current report, with respect to primarily the responses of focal species for the conservation measure, but in some of the areas also ecosystem responses. Five of the NTZs were established in 2009-2011, as part of a government commission, while the other three had been established earlier. The results of the evaluations are presented in a synthesis and also in separate, more detailed chapters for each of the eight NTZs. Overall, the results suggest that NTZs can increase abundances and biomasses of fish and decapod crustaceans, given that the closed areas are strategically placed and of an appropriate size in relation to the life cycle of the focal species. A meta-regression of the effects on focal species of the NTZs showed that CPUE was on average 2.6 times higher after three years of protection, and 3.8 times higher than in the fished reference areas after six years of protection. The proportion of old and large individuals increased in most NTZs, and thereby also the reproductive potential of populations. The increase in abundance of large predatory fish also likely contributed to restoring ecosystem functions, such as top-down control. These effects appeared after a 5-year period and in many cases remained and continued to increase in the longer term (>10 years). In the two areas where cod was the focal species of the NTZs, positive responses were weak, likely as an effect of long-term past, and in the Kattegat still present, recruitment overfishing. In the Baltic Sea, predation by grey seal and cormorant was in some cases so high that it likely counteracted the positive effects of removing fisheries and led to stock declines in the NTZs. In most cases, the introduction of the NTZs has likely decreased the total fishing effort rather than displacing it to adjacent areas. In the Kattegat NTZ, however, the purpose was explicitly to displace an unselective coastal mixed bottom-trawl fishery targeting Norway lobster and flatfish to areas where the bycatches of mature cod were smaller. In two areas that were reopened to fishing after 5 years, the positive effects of the NTZs on fish stocks eroded quickly to pre-closure levels despite that the areas remained closed during the spawning period, highlighting that permanent closures may be necessary to maintain positive effects.We conclude from the Swedish case studies that NTZs may well function as a complement to other fisheries management measures, such as catch, effort and gear regulations. The experiences from the current evaluation show that NTZs can be an important tool for fisheries management especially for local coastal fish populations and areas with mixed fisheries, as well as in cases where there is a need to counteract adverse ecosystem effects of fishing. NTZs are also needed as reference for marine environmental management, and for understanding the effects of fishing on fish populations and other ecosystem components in relation to other pressures. MPAs where the protection of both fish and their habitats is combined may be an important instrument for ecosystembased management, where the recovery of large predatory fish may lead to a restoration of important ecosystem functions and contribute to improving decayed habitats.With the new Biodiversity Strategy, EUs level of ambition for marine conservation increases significantly, with the goal of 30% of coastal and marine waters protected by 2030, and, importantly, one third of these areas being strictly protected. From a conservation perspective, rare, sensitive and/or charismatic species or habitats are often in focus when designating MPAs, and displacement of fisheries is then considered an unwanted side effect. However, if the establishment of strictly protected areas also aims to rebuild fish stocks, these MPAs should be placed in heavily fished areas and designed to protect depleted populations by accounting for their home ranges to generate positive outcomes. Thus, extensive displacement of fisheries is required to reach benefits for depleted populations, and need to be accounted for e.g. by specific regulations outside the strictly protected areas. These new extensive EU goals for MPA establishment pose a challenge for management, but at the same time offer an opportunity to bridge the current gap between conservation and fisheries management.
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| 5. |
- Johansson, Maria U, et al.
(författare)
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Structure, specificity, and mode of interaction for bacterial albumin-binding modules.
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 277:10, s. 8114-8120
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Tidskriftsartikel (refereegranskat)abstract
- We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.
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| 6. |
- Jägetoft, Zebulohn, et al.
(författare)
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Anthropometric measures do not explain the 2D : 4D ratio sexual dimorphism in 7-year-old children
- 2022
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Ingår i: American Journal of Human Biology. - : John Wiley & Sons. - 1042-0533 .- 1520-6300. ; 34:9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Digit ratio (2D:4D) might reflect prenatal testosterone exposure and has been used as a putative marker for androgen related outcomes. However, such associations might be inflicted by confounders. Application of 2D:4D in epidemiological research motivate identification of biological background determinants. We examined sex, anthropometric measures, and maternal factors as determinants of 2D:4D in Swedish 7-year-old children.METHODS: The study was embedded in the Swedish Environmental, Longitudinal, Mother and Child, Asthma and Allergy (SELMA) pregnancy cohort. A total of 870 pre-pubertal children, median 7.5 years of age, were studied. A single assessor performed digit measurements from scanned photocopies using computer software. Child anthropometric measurements investigated were hand size, birthweight, recumbent birth length, standing height, weight, BMI, body fat percentage, and waist/hip circumference. Maternal factors included age, pregnancy length, parity, and education.RESULTS: We found a significant sexual dimorphism regarding digit lengths and 2D:4D, boys on average presenting a lower 2D:4D than girls also after adjustment for summed finger lengths and body fatness. In crude analyses, maternal age correlated with 2D:4D across the whole population and in females but not in adjusted models. No other study variables were associated with 2D:4D.CONCLUSION: Digit ratio showed sexual dimorphism at the age of seven and seems to represent a true sex difference rather than an artifact and bias from hand size, body size or body fat content. Among the rest of our investigated variables, we found no determinants constituting important confounders in future research on 2D:4D ratio.
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| 7. |
- Kronstrand, Robert, et al.
(författare)
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A Cluster of Deaths Involving 5-(2-Aminopropyl)Indole(5-IT)
- 2013
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP): Policy F. - 0146-4760 .- 1945-2403. ; 37:8, s. 542-546
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Tidskriftsartikel (refereegranskat)abstract
- During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 mg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.
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| 8. |
- Metra, Marco, et al.
(författare)
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y Effects of Serelaxin in Patients with Acute Heart Failure
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:8, s. 716-726
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.) In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
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| 9. |
- Nelander, Maria, et al.
(författare)
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Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:10, s. 1212-1218
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. Still we do not know if the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty to examine the cerebral circulation.Material and methodsWe have used a non-invasive diffusion weighted magnetic resonance imaging (MRI) technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant women (n=16). Estimates of cerebral blood volume, blood flow and edema were measured in five different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and grey matter.ResultsExcept for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus we found lower cerebral blood volume and lower blood flow in preeclampsia compared to both normal pregnancy (p=0.01 and p=0.03, respectively) and non-pregnant women (both p=0.02). No differences in edema were detected between study groups.ConclusionThe cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia compared to normal pregnancy and non-pregnant women.
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| 10. |
- Nelander, Maria, et al.
(författare)
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Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study
- 2017
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 30:7, s. 667-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.
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