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- Ranehill, Eva, et al.
(author)
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Hormonal Contraceptives Do Not Impact Economic Preferences: Evidence from a Randomized Trial
- 2018
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In: Management science. - : Institute for Operations Research and the Management Sciences (INFORMS). - 0025-1909 .- 1526-5501. ; 64:10, s. 4471-4965
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Journal article (peer-reviewed)abstract
- A growing body of correlational studies suggests that sex hormones such as those contained in, or affected by, oral contraceptives (OCs) may impact economic behavior. However, despite widespread use of OCs among women in Western countries, little is known about their potential behavioral effects. The present study investigates whether OCs causally influence economic preferences. We randomly allocate 340 women aged 18–35 to three months of a widely used OC or placebo treatment. At the end of treatment, we conduct an economic experiment measuring altruism, financial risk taking, and willingness to compete. The statistical power is 80% to detect an effect size equal to a Cohen’s d of 0.30 at the 5% level. We find no significant effects of OCs on any of the measured preferences, indicating that this widely used OC treatment, commonly used throughout the world, does not significantly affect the measured economic preferences. Further, we find no relation between menstrual cycle phase and economic preferences in the placebo group.
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| 2. |
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| 3. |
- Auffray, Charles, et al.
(author)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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In: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X .- 1756-994X. ; 8:71
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Journal article (peer-reviewed)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 4. |
- Curbo, Sophie, et al.
(author)
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Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides
- 2009
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 390:4, s. 1272-1277
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Journal article (peer-reviewed)abstract
- Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4R alpha receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown to be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family.
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| 5. |
- Hanessian, Stephen, et al.
(author)
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Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa
- 2010
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In: Bioorganic & Medicinal Chemistry Letters. - : Elsevier Ltd. - 0960-894X .- 1464-3405. ; 20:23, s. 6925-6928
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Journal article (peer-reviewed)abstract
- The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases. Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified.
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| 6. |
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| 7. |
- Johannesson, Magnus, et al.
(author)
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Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial
- 2016
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In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press (OUP): Policy B - Oxford Open Option A. - 0021-972X .- 1945-7197. ; 101:11, s. 4046-4053
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Journal article (peer-reviewed)abstract
- Context: There is a lack of knowledge about how oral contraceptives may affect sexual function.Objective: To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality.Design: A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015.Setting: Karolinska University Hospital, Stockholm, Sweden.Participants: A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study.Interventions: A combined oral contraceptive (150 mu g levonorgestrel and 30 mu g ethinylestradiol) or placebo for 3 months of treatment.Main Outcome Measures: The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale.Results: Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P =.032), arousal (-5.1; 95% CI, -9.63 to -0.48; P=.030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P =.036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups.Conclusions: This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.
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| 8. |
- Laine, Veronika N., et al.
(author)
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Whole-genome Analysis Reveals Contrasting Relationships Among Nuclear and Mitochondrial Genomes Between Three Sympatric Bat Species
- 2023
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In: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 15:1
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Journal article (peer-reviewed)abstract
- Understanding mechanisms involved in speciation can be challenging, especially when hybridization or introgression blurs species boundaries. In bats, resolving relationships of some closely related groups has proved difficult due subtle interspecific variation both in morphometrics and molecular data sets. The endemic South American Histiotus bats, currently considered a subgenus of Eptesicus, harbor unresolved phylogenetic relationships and of those is a trio consisting of two closely related species: Eptesicus (Histiotus) macrotus and Eptesicus (Histiotus) montanus, and their relationship with a third, Eptesicus (Histiotus) magellanicus. The three sympatric species bear marked resemblance to each other, but can be differentiated morphologically. Furthermore, previous studies have been unable to differentiate the species from each other at a molecular level. In order to disentangle the phylogenetic relationships of these species, we examined the differentiation patterns and evolutionary history of the three Eptesicus (H.) species at the whole-genome level. The nuclear DNA statistics between the species suggest strong gene flow and recent hybridization between E. (H.) montanus and E. (H.) macrotus, whereas E. (H.) magellanicus shows a higher degree of isolation. In contrast, mitochondrial DNA shows a closer relationship between E. (H.) magellanicus and E. (H.) montanus. Opposing patterns in mtDNA and nuclear markers are often due to differences in dispersal, and here it could be both as a result of isolation in refugia during the last glacial maximum and female philopatry and male-biased dispersal. In conclusion, this study shows the importance of both the nuclear and mitochondrial DNA in resolving phylogenetic relationships and species histories.
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| 10. |
- Masjedi, Khosro, 1969-
(author)
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In vitro analyses of immune responses to metal and organic haptens in humans with contact allergy
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Contact allergy is one of the most common skin diseases with great social and economical impact. The origin and nature of contact allergens (haptens) capable of inducing T-cell mediated allergic reactions are diverse, ranging from organic molecules to metal ions. Most of the current knowledge on T-cell responses to haptens in humans with contact allergy have been established by studies on the metal ion nickel (Ni), the most common cause of contact allergy, whereas reactivity to the large group of organic haptens has been less studied.Haptens are not immunogenic by themselves but must bind carrier molecules prior to their presentation on MHC class I or II molecules and subsequent recognition by T cells. Due to differences in their chemical nature, haptens interact with host molecules by different mechanisms and differences in their solubility can influence their access to different antigen-presenting pathways.The aim of the present study was to define immune responses elicited by haptens of different chemical nature including Ni (hydrophilic metal ion), methylisothiazolinones (hydrophilic organic molecule) and parthenolide (lipophilic organic molecule). The immune response displayed by subjects with allergy to these substances, and non-allergic control subjects, was assessed by measuring hapten-induced cytokine production in peripheral blood mononuclear cells (PBMC) with a focus on ELISpot analysis of T-cell type 1 (e.g. IFN-g and IL-2) and type 2 (e.g. IL-4, IL-5 and IL-13) cytokines. For Ni and parthenolide, the phenotype of the hapten-reactive T cells was determined. The allergic status of subjects was defined by clinical history and patch testing. The latter is the established diagnostic method for contact allergy, based on applying various haptens to the subjects’ back and grading the skin reaction after 2-3 days.All three haptens elicited a concomitant T-cell type 1 and 2 response in subjects with contact allergy to the corresponding hapten, suggesting the induction of a functionally related cytokine profile, irrespective of the chemical character of the hapten. The cytokine response was related to the degree of the subjects’ patch test reactivity; PBMC from a vast majority of subjects with strong and moderate patch test reactivity displayed detectable cytokine responses to the corresponding haptens, whereas subjects with weak or no (controls) patch test reactivity did not. Despite the similar cytokine profile induced, the phenotype of the reactive T cells was found to differ between haptens with Ni eliciting CD4+ T cells and parthenolide eliciting CD8+ T cells. This difference may be explained by a better ability of a lipophilic hapten to gain access to the MHC class I-restricted antigen-presentation pathway. Moreover, the data suggest that analysis of cytokine responses to haptens may facilitate future development of in vitro-based diagnostics assay for contact allergy.Finally, the relationship between the variation over time in patch test reactivity and systemic reactivity to Ni, in terms of cytokine responses to Ni in vitro, was investigated. The degree of patch test reactivity is known to vary over time, in particular in subjects with weak reactivity. Ni-allergic subjects were patch tested three times with three month intervals and PBMC obtained at the same time points were assessed for in vitro reactivity to Ni. The overall reactivity in the patch test and the in vitro test was well correlated confirming that both methods provide a good and comparable estimate of the systemic reactivity to Ni. However, fluctuations in the patch test reactivity over time were not well correlated with variations in the cytokine response elicited in vitro suggesting that other parameters besides changes in the systemic reactivity could significantly contribute to the variation in patch test reaction over time.
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