| 1. |
- Axfors, Cathrine, et al.
(author)
-
Cohort profile : the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort
- 2019
-
In: BMJ Open. - : BMJ. - 2044-6055. ; 9:10
-
Journal article (peer-reviewed)abstract
- PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system.FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.
|
|
| 2. |
- Bränn, Emma, 1988-, et al.
(author)
-
Metabolic Profiling Indicates Diversity in the Metabolic Physiologies Associated With Maternal Postpartum Depressive Symptoms
- 2021
-
In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Postpartum depression (PPD) is a devastating disease requiring improvements in diagnosis and prevention. Blood metabolomics identifies biological markers discriminatory between women with and those without antenatal depressive symptoms. Whether this cutting-edge method can be applied to postpartum depressive symptoms merits further investigation. Methods: As a substudy within the Biology, Affect, Stress, Imagine and Cognition Study, 24 women with PPD symptom (PPDS) assessment at 6 weeks postpartum were included. Controls were selected as having a score of ≤ 6 and PPDS cases as ≥12 on the Edinburgh Postnatal Depression Scale. Blood plasma was collected at 10 weeks postpartum and analyzed with gas chromatography-mass spectrometry metabolomics. Results: Variations of metabolomic profiles within the PPDS samples were identified. One cluster showed altered kidney function, whereas the other, a metabolic syndrome profile, both previously associated with depression. Five metabolites (glycerol, threonine, 2-hydroxybutanoic acid, erythritol, and phenylalanine) showed higher abundance among women with PPDSs, indicating perturbations in the serine/threonine and glycerol lipid metabolism, suggesting oxidative stress conditions. Conclusions: Alterations in certain metabolites were associated with depressive pathophysiology postpartum, whereas diversity in PPDS physiologies was revealed. Hence, plasma metabolic profiling could be considered in diagnosis and pathophysiological investigation of PPD toward providing clues for treatment. Future studies require standardization of various subgroups with respect to symptom onset, lifestyle, and comorbidities.
|
|
| 3. |
|
|
| 4. |
- Amsteus, Martin, 1972-, et al.
(author)
-
The Sound of Choice
- 2016
-
In: International Journal of Business and Social Science. - : Center for Promoting Ideas. - 2219-1933. ; 7:1, s. 42-49
-
Journal article (peer-reviewed)abstract
- The purpose of this study is to testthe effect of suggestive music on consumer choice in cafés. It is proposed that suggestive music influences consumer choice in cafés. The hypotheses were tested through Chi-square on a totalof 283 measures. The results show that suggestive music has an effect on consumer choice in cafés. Managers who want to influence consumer choice in cafés through suggestive music may be able to do so. The results provide empirical support for the idea that suggestive music and the associations it carries represent information that consumers use for assessing choices and making selections.
|
|
| 5. |
- Axling, Ulrika, et al.
(author)
-
Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program
- 2011
-
In: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. 111-121
-
Journal article (peer-reviewed)abstract
- Andersson U, Henriksson E, Strom K, Alenfall J, Goransson O, Holm C. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. Am J Physiol Endocrinol Metab 300: E111-E121, 2011. First published October 19, 2010; doi:10.1152/ajpendo.00268.2010.-The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.
|
|
| 6. |
- Berggreen, Christine, et al.
(author)
-
cAMP-elevation mediated by β-adrenergic stimulation inhibits salt-inducible kinase (SIK) 3 activity in adipocytes.
- 2012
-
In: Cellular Signalling. - : Elsevier BV. - 1873-3913 .- 0898-6568. ; 24:9, s. 1863-1871
-
Journal article (peer-reviewed)abstract
- Salt-inducible kinase (SIK) 3 is a virtually unstudied, ubiquitously expressed serine/threonine kinase, belonging to the AMP-activated protein kinase (AMPK)-related family of kinases, all of which are regulated by LKB1 phosphorylation of a threonine residue in their activation (T)-loops. Findings in adrenal cells have revealed a role for cAMP in the regulation of SIK1, and recent findings suggest that insulin can regulate an SIK isoform in Drosophila. As cAMP has important functions in adipocytes, mainly in the regulation of lipolysis, we have evaluated a potential role for cAMP, as well as for insulin, in the regulation of SIK3 in these cells. We establish that raised cAMP levels in response to forskolin and the β-adrenergic receptor agonist CL 316,243 induce a phosphorylation of SIK3 in HEK293 cells and primary adipocytes. This phosphorylation coincides with increased 14-3-3 binding to SIK3 in these cell types. Our findings also show that cAMP-elevation results in reduced SIK3 activity in adipocytes. Phosphopeptide mapping and site-directed mutagenesis reveal that the cAMP-mediated regulation of SIK3 appears to depend on three residues, T469, S551 and S674, that all contribute to some extent to the cAMP-induced phosphorylation and 14-3-3-binding. As the cAMP-induced regulation can be reversed with the protein kinase A (PKA) inhibitor H89, and a role for other candidate kinases, including PKB and RSK, could be excluded, we believe that PKA is the kinase responsible for SIK3 regulation in response to elevated cAMP levels. Our findings of cAMP-mediated regulation of SIK3 suggest that SIK3 may mediate some of the effects of this important second messenger in adipocytes.
|
|
| 7. |
|
|
| 8. |
- Bonagas, Nadilly, et al.
(author)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
|
|
| 9. |
- Brulin, Emma, et al.
(author)
-
An impaired learning environment : Resident physicians’ experience of the transition to pandemic care during the first wave of the COVID-19 pandemic in Sweden
- 2023
-
In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
-
Journal article (peer-reviewed)abstract
- Introduction: Extensive studies regarding the COVID-19 pandemic have shown negative effects on physicians-in-training. Besides a high workload, their learning environment has been affected. A quality learning environment is vital for residents’ physician’s clinical development and also their health. Nevertheless, few studies have explored this. The aim of this study was to explore resident physicians’ experiences of transition to pandemic care during the first wave of the COVID-19 pandemic in Sweden. Method: In this qualitative study, 12 Swedish resident physicians were interviewed using a semi-structured interview guide. They were interviewed between June and October of 2020 and asked to reflect on the pandemic and, more specifically, the first wave. The empirical material was analysed using qualitative content analysis. The analysis resulted in one theme and four categories. Results: The theme identified was An impaired learning environment which signifies the disruptions the resident physicians experienced during the first wave of the pandemic. The four categories, Professional role insecurity, High expectations but little influence, Stagnant clinical development, and Professional growth through experience, describe in what way the learning environment was impacted.
|
|
| 10. |
- Chotiwan, Nunya, et al.
(author)
-
Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combine multimodal imaging (cm-nm scale) with single nuclei RNA-sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar-/-) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection is imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection is limited to grey matter of sensory systems in wildtype mice, but extends into white matter, meninges and choroid plexus in Ifnar-/- mice. Cells in wildtype display strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+ NK cells, whereas in Ifnar-/-, the absence of this response contributes to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.
|
|
| 11. |
- Efe, C., et al.
(author)
-
Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
-
In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
|
|
| 12. |
- Gormand, Amelie, et al.
(author)
-
Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.
- 2011
-
In: Journal of Cellular Biochemistry. - : Wiley. - 0730-2312. ; 112, s. 1364-1375
-
Journal article (peer-reviewed)abstract
- AMP-activated protein kinase (AMPK) is a serine/threonine kinase that regulates cellular and whole body energy homeostasis. In adipose tissue, activation of AMPK has been demonstrated in response to a variety of extracellular stimuli. However, the upstream kinase that activates AMPK in adipocytes remains elusive. Previous studies have identified LKB1 as a major AMPK kinase in muscle, liver and other tissues. In certain cell types, Ca(2+) /Calmodulin-dependent protein kinase kinase (CaMKK) β has been shown to activate AMPK in response to increase of intracellular Ca(2+) levels. Our aim was to investigate if LKB1 and/or CaMKK function as AMPK kinases in adipocytes. We used adipose tissue and isolated adipocytes from mice in which the expression of LKB1 was reduced to 10-20% of that of wild-type (LKB1 hypomorphic mice). We show that adipocytes from LKB1 hypomorphic mice display a 40% decrease in basal AMPK activity and a decrease of AMPK activity in the presence of the AMPK activator phenformin. We also demonstrate that stimulation of 3T3L1 adipocytes with intracellular [Ca(2+) ]-raising agents results in an activation of the AMPK pathway. The inhibition of CaMKK isoforms, particularly CaMKKβ, by the inhibitor STO-609 or by siRNAs, blocked Ca(2+) -, but not phenformin-, AICAR or forskolin-induced activation of AMPK, indicating that CaMKK activated AMPK in response to Ca(2+) . Collectively, we show that LKB1 is required to maintain normal AMPK-signalling in non-stimulated adipocytes and in the presence of phenformin. In addition, we demonstrate the existence of a Ca(2+) /CaMKK signalling pathway that can also regulate the activity of AMPK in adipocytes. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.
|
|
| 13. |
- Henriks, Göran, et al.
(author)
-
Skapa en kultur med patienten som en aktiv partner
- 2015
-
In: Kvalitetsmässan 2015, 3-5 november 2015, Göteborg, Sverige..
-
Conference paper (other academic/artistic)abstract
- Utgångspunkten i personcentrerad vård är att utgå från att alla människor som arbetar inom vård och omsorg är kapabla att ta ansvar för sig själva och sitt arbete. Men hur styr man en verksamhet som drivs av berättelser, lyssnande, överenskommelser och dokumentationer? Är det styrning underifrån, ovanifrån eller genom partnerskap? Det är en utmaning att leda en verksamhet som involverar patienten som aktiv partner och en del av vårdteamet.
|
|
| 14. |
|
|
| 15. |
- Henriksson, Emma
(author)
-
LKB1 signaling pathways in adipocytes - Focus on the AMPK-related kinase SIK2
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Adipose tissue does not only store and release energy in response to hormones, it is also known as an endocrine organ, secreting important factors and hormones that influence for example appetite and insulin sensitivity. The association of type 2 diabetes with obesity has been known for quite some time. Understanding the cellular mechanisms of adipocyte function is of great importance in understanding when and why excess adipose tissue becomes dangerous. Signal transduction pathways used for example by hormones to control cellular function, often consists of protein kinases. These enzymes constitute a large part of our genome and are crucial for the regulation of almost all cellular processes. AMP-activated protein kinase (AMPK) is known for its various roles in the regulation of metabolism and is activated when cellular energy levels are low, which is reflected in increased levels of AMP. In addition to AMPK, some of its related kinases, including the salt-inducible kinases (SIKs), have also been implicated in the regulation of metabolism. LKB1 is known as a tumor suppressor and was recently found to be required for the activity of AMPK and most of its related kinases, phosphorylating a specific threonine residue in their activation loop. The aim of this thesis was to investigate the regulation of LKB1 signaling pathways in adipocytes, with a focus on SIK2, which is of particulate interest in adipocytes due to its high abundance in these cells. We show that AMPK activity is regulated by LKB1 and CaMKK in adipocytes and describe a regulation of SIK2 and SIK3 by cAMP/PKA signaling. The PKA-dependent phosphorylations of SIK2 and SIK3 were identified and shown to mediate a binding to 14-3-3 proteins, resulting in a re-localization from a particulate fraction to the cytosol, and a decrease in activity, respectively. In addition, we suggest that the transcriptional regulators CREB-regulated transcription co-activator (CRTC) 2, -3 and histone deacetylase (HDAC) 4, are substrates of SIK2 in adipocytes. Based on our findings, we hypothesize that SIK isoforms take part in transcriptional regulation of genes involved in lipid and glucose metabolism in adipocytes, through their action on HDAC4, CRTC2 and CRTC3, and potentially also other transcriptional regulators. We also identified PP2A as an interacting partner of SIK2 in adipocytes and future studies will further evaluate the importance and function of this interaction. In conclusion, this thesis has revealed regulation of AMPK, SIK2 and SIK3, important for adipocyte function and provided preliminary data connecting SIK2 to both lipid and glucose metabolism in adipocytes.
|
|
| 16. |
- Henriksson, Emma, et al.
(author)
-
SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes
- 2015
-
In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 128:3, s. 472-486
-
Journal article (peer-reviewed)abstract
- Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2-CRTC2-HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP-PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.
|
|
| 17. |
- Henriksson, Emma, et al.
(author)
-
The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser(358) in adipocytes
- 2012
-
In: Biochemical Journal. - 0264-6021. ; 444, s. 503-514
-
Journal article (peer-reviewed)abstract
- SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein kinase) family of kinases and is highly expressed in adipocytes. We investigated the regulation of SIK2 in adipocytes in response to cellular stimuli with relevance for adipocyte function and/or AMPK signalling. None of the treatments, including insulin, cAMP inducers or AICAR (5-amino-4-imidazolecarboxamide riboside), affected SIK2 activity towards peptide or protein substrates in vitro. However, stimulation with the cAMP-elevating agent forskolin and the beta-adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)-dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of SIK2 revealed several sites phosphorylated in response to cAMP induction, including Ser(358). Site-directed mutagenesis demonstrated that phosphorylation of See(358), but not the previously reported PKA site See(587), was required for 14-3-3 binding. Immunocytochemistry illustrated that the localization of exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation of adipocytes, however, revealed a significant increase of wild-type, but not Ser358Ala, HA (haemagglutinin) SIK2 in the cytosol and a concomitant decrease in a particulate fraction after CL 316,243 treatment. This supports a phosphorylation-dependent relocalization in adipocytes. We hypothesize that regulation of SIK2 by cAMP could play a role for the critical effects of this second messenger on lipid metabolism in adipocytes.
|
|
| 18. |
- Henriksson, Hanna E., et al.
(author)
-
Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms
- 2019
-
In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9
-
Journal article (peer-reviewed)abstract
- Antenatal depression affects similar to 9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.
|
|
| 19. |
- Henriksson, Hanna E., et al.
(author)
-
Spring peaks and autumn troughs identified in peripheral inflammatory markers during the peripartum period
- 2019
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 15328-
-
Journal article (peer-reviewed)abstract
- Seasonal variations have recently been described in biomarkers, cell types, and gene expression associated with the immune system, but so far no studies have been conducted among women in the peripartum period. It is of note that pregnancy complications and outcomes, as well as autoimmune diseases, have also been reported to exhibit seasonal fluctuations. We report here a clear-cut seasonal pattern of 23 inflammatory markers, analysed using proximity-extension assay technology, in pregnant women. The inflammatory markers generally peaked in the spring and had a trough in the autumn. During the postpartum period we found seasonality in one inflammatory marker, namely monocyte chemotactic protein 4 (MCP-4). Our findings suggest that seasonal variations in peripheral inflammatory markers are only observed during pregnancy. The results of this study could be valuable to professionals working within the field of immunology-related areas, and provide insight for the understanding of obstetric complications.
|
|
| 20. |
- Henriksson, Jessica, 1987-, et al.
(author)
-
Effects of Eight-Week-Web-Based Mindfulness Training on Pain Intensity, Pain Acceptance, and Life Satisfaction in Individuals With Chronic Pain
- 2016
-
In: Psychological Reports. - : Sage Publications. - 0033-2941 .- 1558-691X. ; 119:3, s. 586-607
-
Journal article (peer-reviewed)abstract
- This study examined the effects of an eight-week-web-based mindfulness programdesigned for individuals with chronic pain. A sample of 107 participants with chronicpain (M¼51.0 years, SD¼9.3) were randomly assigned to a treatment group and acontrol group. The mindfulness program involved 20 minutes of training per day, sixdays a week, for eight weeks. During this period, the control group was invited to anonline discussion forum involving pain-related topics. A total of 77 participantscompleted the postintervention assessment (n¼36 in the treatment group, n¼41in the control group). The group assigned to mindfulness training showed increasedmindfulness skills (Cohen’s d¼1.18), reduced pain intensity (d¼0.47–0.82), reducedpain-related interference/suffering (d¼0.39–0.85), heightened pain acceptance(d¼0.66), reduced affective distress (d¼0.67), and higher ratings of life satisfaction(d¼0.54) following the training with no or minor changes up for the control group(d values 0.01–0.23), a pattern substantiated by significant group-by-time interactions.Despite limitations of this study, including a less than ideal control groupto isolate effects of mindfulness and lack of a long-term follow-up, the results appearpromising and may motivate further investigations.
|
|
| 21. |
- Henriksson, Malin, 1981-, et al.
(author)
-
"Om nåt skulle hända" : Ett gestaltningsprojekt om ungas upplevelser av otrygghet i utemiljöer
- 2016
-
Reports (pop. science, debate, etc.)abstract
- Under 2016 producerade Statens väg- och transportforskningsinstitut (VTI) tillsammans med Östergötlands museum en vandringsutställning om ungas upplevelser av otrygghet. Projektet finansierades av Boverket inom utlysningen ”stöd till utvecklingsprojekt för jämställda offentliga miljöer i städer och tätorter”. Projektet utgår från problematiken att ungdomars upplevelser av otrygghet sällan kommer till uttryck i stadsplaneringen. Inte heller i forskningen om upplevelser av våld och otrygghet i det offentliga rummet uppmärksammas ungdomar i särskilt hög grad. Samtidigt förflyttar sig ungdomar som grupp mer än andra grupper och vistas i högre grad utomhus. De är också utomhus på andra tidpunkter än vuxna, på kvällen och natten. Vidare är ungdomar, oavsett kön, mer utsatta för våld utomhus än andra grupper. Det är därför att utveckla nya verktyg för att belysa ungdomars erfarenheter av otrygghet i utomhusmiljöer.Underlaget för utställningen utgjordes av gruppintervjuer med ett fyrtiotal ungdomar (killar, tjejer och transpersoner) mellan 13 och 20 år. Den feministiska metoden minnesarbete användes för att underlätta samtal om trygghet, otrygghet och rädsla. Metoden går ut på att deltagarna i en grupp skriver individuella minnen på ett på förhand bestämt tema. Minnena tolkas sedan kollektivt i gruppen.Intervjuerna tolkades och bearbetades av projektgruppen. Utifrån tolkningsprocessen gestaltades ungdomarnas erfarenheter dels fotografiskt och dels i text. Fyra fiktiva karaktärer togs fram och i utställningen får besökaren följa dem hem. Milo, David, Jo och Semira har alla olika erfarenheter och upplever olika moment i staden och hemresan som otrygga. Vidare togs en pedagogisk handledning fram. Den pedagogiska handledningen innehåller förslag på övningar som fördjupar utställningens teman. Den fungerar som ett stöd för skolor som hyr utställningen och kan användas av lärare i undervisningen. Pedagoger från Östergötlands museum kan vidare leda lektioner som bygger på handledningen om skolan så önskar.Projektet avslutades med en fyra veckor lång turné där ungdomar i olika åldrar fick ta del av utställningen och arbeta med den pedagogiskt. Turnén utvärderades med genomgående goda resultat.Projektet bidrar avslutningsvis till att stärka planeringen av jämställda miljöer på två sätt. För det första ger utställningen insikter om hur unga människor upplever trygghet i utemiljöer. För det andra är utställningen ett verktyg som gör det möjligt att praktiskt arbeta med frågorna pedagogiskt i skolmiljöer, eller i stadsplaneringssammanhang med planerare och andra aktörer.
|
|
| 22. |
- Johansson, Birgitta, 1959-, et al.
(author)
-
The effect of internet-administered support (carer eSupport) on preparedness for caregiving in informal caregivers of patients with head and neck cancer compared with support as usual: a study protocol for a randomized controlled trial.
- 2024
-
In: BMC cancer. - 1471-2407. ; 24:1
-
Journal article (peer-reviewed)abstract
- Informal caregivers (ICs) of patients with cancer provide essential and mainly uncompensated care. A self-perceived preparedness to care for the patient is associated with a lower caregiver burden, described as the extent to which caregiving is perceived as having adverse effects on IC functioning and well-being. ICs' well-being is associated with patient-perceived quality of care, suggesting that interventions to optimize ICs' health are essential in order to improve patient care. Head and neck cancer (HNC) is the seventh most common malignant disease in the world. The disease and its treatment have a significant negative impact on the patient's health and quality of life. Symptoms usually interfere with swallowing, food and fluid intake, breathing, speaking, and communication. ICs frequently manage patients' symptoms and side effects, especially problems related to nutrition and oral pain, without being properly prepared. Carer eSupport is an Internet-administered intervention, based on focus group discussions with ICs, developed in collaboration with ICs and healthcare professionals, tested for feasibility, and deemed feasible. This study protocol outlines the methods of investigating the effects of Carer eSupport plus support as usual (SAU) on self-reported preparedness for caregiving, caregiver burden, and well-being in the ICs of patients with HNC, compared with ICs receiving SAU only.In this randomized controlled trial, 110 ICs of patients with HNC, undergoing radiotherapy combined with surgery and/or medical oncological treatment, will be randomized (1:1) to Carer eSupport plus SAU or SAU only. Data will be collected at baseline (before randomization), post-intervention (after 18 weeks), and 3 months after post-intervention. The primary outcome is self-reported preparedness for caregiving. Secondary outcomes are self-reported caregiver burden, anxiety, depression, and health-related quality of life. The effect of Carer eSupport plus SAU on preparedness for caregiving and secondary outcomes, compared with SAU only, will be evaluated by intention to treat analyses using linear regression models, mixed-model regression, or analysis of covariance.If proven effective, Carer eSupport has the potential to significantly improve ICs' preparedness for caregiving and their wellbeing, thereby improving patient-perceived quality of care and patient wellbeing.ClinicalTrials.gov; NCT06307418, registered 12.03.2024 (https://clinicaltrials.gov/search? term=NCT06307418).
|
|
| 23. |
- Jungebluth, Philipp, et al.
(author)
-
Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite : a proof-of-concept study
- 2011
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9808, s. 1997-2004
-
Journal article (peer-reviewed)abstract
- Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.
|
|
| 24. |
- Karimi, Masoud, et al.
(author)
-
A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families
- 2018
-
In: Hereditary Cancer in Clinical Practice. - : BMC. - 1731-2302 .- 1897-4287. ; 16
-
Journal article (peer-reviewed)abstract
- BackgroundLynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.MethodsData were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population.ResultsA total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.ConclusionLynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
|
|
| 25. |
- Karimi, Masoud, et al.
(author)
-
A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 11 Medical and Health Sciences 1117 Public Health and Health Services
- 2018
-
In: Hereditary Cancer in Clinical Practice. - : Springer Science and Business Media LLC. - 1731-2302 .- 1897-4287. ; 16:1
-
Journal article (peer-reviewed)abstract
- Background: Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families. Methods: Data were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population. Results: A total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations. Conclusion: Lynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
|
|
| 26. |
- Kehoe, Laura, et al.
(author)
-
Make EU trade with Brazil sustainable
- 2019
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Journal article (other academic/artistic)
|
|
| 27. |
- Kjellén, Emma, 1984, et al.
(author)
-
Aphasia and literacy - the insider's perspective
- 2017
-
In: International Journal of Language and Communication Disorders. - : Wiley. - 1368-2822 .- 1460-6984. ; 52:5, s. 573-584
-
Journal article (peer-reviewed)abstract
- © 2016 The Authors International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.Background: Few studies have investigated how people with aphasia (PWA) experience literacy skills. Taking the insider's perspective is a way to increase understanding of the individual experiences of literacy among PWA, which may have clinical implications. Aims: To describe how literacy, i.e., reading and writing, is experienced in everyday life by PWA and to gain insight into the part played by literacy skills in their lives. Methods & Procedures: A qualitative descriptive research approach was taken. In-depth interviews were conducted with 12 PWA (six women and six men) who had all lived with aphasia for at least 6 months post-stroke. The interviews were analysed using qualitative content analysis. Outcomes & Results: One overarching theme emerged from the data: literacy as an ongoing recovery process. Based on this overarching theme, two subthemes were identified: changes in conditions for literacy (experiences of reading and writing initially post-onset compared with experiences at the time of the interview); and facing expectations about literacy (participants' own and other people's expectations of them in terms of literacy). Conclusions & Implications: The findings are important at a general level in that they indicate that PWA are able to articulate their individual experiences and thoughts about literacy, i.e., reading and writing. Specifically, PWA in this study experience literacy as playing an essential part in their lives and the findings imply that personal experiences are important in the design of reading and writing interventions in speech and language therapy.
|
|
| 28. |
- Ladds, Marcus J. G. W., et al.
(author)
-
A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Journal article (peer-reviewed)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
|
|
| 29. |
- Master, Emma, et al.
(author)
-
Recombinant Expression and Enzymatic characterization of PttCel9A, a KOR homologue from Populus tremula x tremuloides
- 2004
-
In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 43:31, s. 10080-10089
-
Journal article (peer-reviewed)abstract
- PttCel9A is a membrane-bound, family 9 glycosyl hydrolase from Populus tremula x tremuloides that is upregulated during secondary cell wall synthesis. The catalytic domain of PttCel9A, Delta(1-105)PttCel9A, was purified, and its activity was compared to TfCel9A and TfCel9B from Thermobifida fusca. Since aromatic amino acids involved in substrate binding at subsites -4, -3, and -2 are missing in PttCel9A, the activity of TfCel9A mutant enzymes W256S, W209A, and W313G was also investigated. Delta(1-105)PttCel9A hydrolyzed a comparatively narrow range of polymeric substrates, and the preferred substrate was (carboxymethyl)cellulose 4M. Moreover, Delta(1-105)PttCel9A did not hydrolyze oligosaccharides shorter than cellopentaose, whereas TfCel9A and TfCel9B hydrolyzed cellotetraose and cellotriose, respectively. These data suggest that the preferred substrates of PttCel9A are long, low-substituted, soluble cellulosic polymers. At 30degreesC and pH 6.0, the k(cat) for cellohexaose of Delta(1-105)PttCel9A, TfCel9A, and TfCel9B were 0.023 +/- 0.001, 16.9 +/- 2.0, and 1.3 +/- 0.2, respectively. The catalytic efficiency (k(cat)/K-m) of TfCel9B was 39% of that of TfCel9A, whereas the catalytic efficiency of Delta(1-105)PttCel9A was 0.04% of that of TfCel9A. Removing tryptophan residues at subsites -4, -3, and -2 decreased the efficiency of cellohexaose hydrolysis by TfCel9A. Mutation of W313 to G had the most drastic effect, producing a mutant enzyme with 1% of the catalytic efficiency of TfCel9A. The apparent narrow substrate range and catalytic efficiency of PttCel9A are correlated with a lack of aromatic amino acids in the substrate binding cleft and may be necessary to prevent excessive hydrolysis of cell wall polysaccharides during cell wall formation.
|
|
| 30. |
- Michel, M., et al.
(author)
-
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
-
In: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
-
Journal article (peer-reviewed)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
|
|
| 31. |
- Michelsen, Halldora Ögmundsdottir, et al.
(author)
-
Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study.
- 2023
-
In: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 371, s. 40-48
-
Journal article (peer-reviewed)abstract
- Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI.In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n=7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8mmol/L, blood pressure (BP) <140/90mmHg and smoking abstinence.The strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78-2.50]; 2.45 [1.91-2.99]), having a psychologist in the CR team (1.62 [1.36-1.87]; 2.05 [1.67-2.44]), extended opening hours (2.13 [2.00-2.27]; 1.50 [0.91-2.10]), adequate facilities (1.54 [0.91-2.18]; 1.89 [1.38-2.40]), and having a medical director (1.70 [0.91-2.48]; 1.46 [1.04-1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39-4.51]) and having no history of hypertension (2.93 [2.60-3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66-2.10]; 1.46 [1.14-1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95-2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07-2.88]) and group education (1.92 [1.43-2-42]), and no cardiovascular disease history (2.13 [1.78-2.48]).We identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.
|
|
| 32. |
|
|
| 33. |
- Planting-Bergloo, Sara, 1978-, et al.
(author)
-
Att utveckla elevers förmåga att formulera undersökningsbara frågor i naturvetenskap : Mangling av en didaktisk modell
- 2021
-
In: LUMAT. - : LUMA Centre Finland. - 2323-7112. ; 9:1, s. 774-803
-
Journal article (peer-reviewed)abstract
- En viktig målsättning för naturvetenskaplig undervisning är att utveckla förmågan att formulera undersökningsbara frågor. Syftet med den här studien är att undersöka hur undervisning som utformats med hjälp av metoden Question Formulation Technique (QFT) kan stödja utveckling av elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor. QFT är en modell för att utveckla elevers förmåga att formulera och värdera sina egna frågor i allmänhet. I studien prövas QFT i en svensk skolkontext och inom ramen för naturvetenskaplig undervisning. Studien genomfördes som en interventionsstudie i gymnasieskolan och inom ramen för kursen Gymnasiearbete. I kursen ska eleverna genomföra en egen naturvetenskaplig undersökning. QFT användes för att utforma undervisning som del av introduktionen till kursen. Data består av videoinspelningar av elevsamtal från undervisning som har analyserats utifrån ett pragmatiskt ramverk med organiserande syften och praktisk epistemologisk analys. Resultaten visar vilka närliggande syften som etableras i elevernas samtal om undersökningsbara frågor i undervisningen: (A) att producera så många frågor som möjligt, (B) att bedöma vilka frågor som är mest relevanta, (C) att kategorisera frågor, (D) att hitta och specificera ett undersökningsobjekt och (E) att planera för att genomföra en undersökning. Slutsatsen är att QFT kan fungera som stöd för lärares planering av undervisning om naturvetenskapligt undersökningsbara frågor under förutsättning att läraren aktivt stödjer eleverna i att uppmärksamma centrala kvaliteter avseende undersökningsbarhet och genom att binda samman närliggande syften med det övergripande syftet.
|
|
| 34. |
- Roberts, Neil A., et al.
(author)
-
Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder
- 2019
-
In: Kidney International. - : ELSEVIER SCIENCE INC. - 0085-2538 .- 1523-1755. ; 95:5, s. 1138-1152
-
Journal article (peer-reviewed)abstract
- Mutations in leucine-rich-repeats and immunoglobulin-likedomains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.
|
|
| 35. |
- Scaletti, Emma Rose, et al.
(author)
-
The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors
- 2022
-
In: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 17:18
-
Journal article (peer-reviewed)abstract
- Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial 1-carbon metabolism enzyme, which is an attractive anticancer drug target as it is highly upregulated in cancer but is not expressed in healthy adult cells. Selective MTHFD2 inhibitors could therefore offer reduced side-effects during treatment, which are common with antifolate drugs that target other 1C-metabolism enzymes. This task is challenging however, as MTHFD2 shares high sequence identity with the constitutively expressed isozymes cytosolic MTHFD1 and mitochondrial MTHFD2L. In fact, one of the most potent MTHFD2 inhibitors reported to date, TH7299, is actually more active against MTHFD1 and MTHFD2L. While structures of MTHFD2 and MTHFD1 exist, no MTHFD2L structures are available. We determined the first structure of MTHFD2L and its complex with TH7299, which reveals the structural basis for its highly potent MTHFD2L inhibition. Detailed analysis of the MTHFD2L structure presented here clearly highlights the challenges associated with developing truly isoform-selective MTHFD2 inhibitors.
|
|
| 36. |
|
|
| 37. |
- Svennberg, Emma, et al.
(author)
-
N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation
- 2017
-
In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:16, s. 1271-1277
-
Journal article (peer-reviewed)abstract
- Objective Screening for atrial fibrillation (AF) in individuals aged 65 and above is recommended by the European Society of Cardiology. Increased levels of the biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has in cohort studies been associated with incident AF. The aim of this study was to assess whether NT-proBNP could be useful for AF detection in systematic screening.Methods The Strokestop study entailed 7173 Swedish residents aged 75/76 that were screened for AF using twice daily intermittent ECG recordings during 2 weeks. In a substudy of 886 participants, the last 815 consecutive participants and 71 individuals with newly detected AF, levels of NT-proBNP were determined.Results Participants with newly detected AF (n=96) had a median NT-proBNP of 330 ng/L (IQR 121; 634). In individuals without AF (n=742), median NT-proBNP was 171 ng/L (IQR 95; 283), p<0.001. The CHA2DS2-VASc parameters did not differ significantly between individuals with newly detected AF and without AF nor between newly detected AF in the NT-proBNP cohort compared with the cohort where NT-proBNP was not assessed. Using an NT-proBNP cut-off of >= 125 ng/L in a non-acute setting yielded a negative predictive value of 92%, meaning that 35% fewer participants would need to be screened when applied to systematic AF screening. Adding weight to NT-proBNP further reduced participants needed to be screened with a preserved sensitivity.Conclusions NT-proBNP was increased in individuals with newly detected AF. Prospective studies could clarify if NT-proBNP can be used to correctly select individuals that benefit most from AF screening.
|
|
| 38. |
- Säll, Johanna, et al.
(author)
-
Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals : implications for insulin signalling and glucose uptake in human adipocytes
- 2017
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:2, s. 314-323
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose uptake in human adipocytes.METHODS: SIK mRNA and protein was determined in human adipose tissue or adipocytes, and correlated to clinical variables. SIK2 and SIK3 expression and phosphorylation were analysed in adipocytes treated with TNF-α. Glucose uptake, GLUT protein levels and localisation, phosphorylation of protein kinase B (PKB/Akt) and the SIK substrate histone deacetylase 4 (HDAC4) were analysed after the SIKs had been silenced using small interfering RNA (siRNA) or inhibited using a pan-SIK-inhibitor (HG-9-91-01).RESULTS: We demonstrate that SIK2 and SIK3 mRNA are downregulated in adipose tissue from obese individuals and that the expression is regulated by weight change. SIK2 is also negatively associated with in vivo insulin resistance (HOMA-IR), independently of BMI and age. Moreover, SIK2 protein levels and specific kinase activity display a negative correlation to BMI in human adipocytes. Furthermore, SIK2 and SIK3 are downregulated by TNF-α in adipocytes. Silencing or inhibiting SIK1-3 in adipocytes results in reduced phosphorylation of HDAC4 and PKB/Akt, less GLUT4 at the plasma membrane, and lower basal and insulin-stimulated glucose uptake in adipocytes.CONCLUSION/INTERPRETATION: This is the first study to describe the expression and function of SIKs in human adipocytes. Our data suggest that SIKs might be protective in the development of obesity-induced insulin resistance, with implications for future treatment strategies.
|
|
| 39. |
|
|
| 40. |
- Wichardt, Emma, et al.
(author)
-
Rhabdomyolysis/myoglobinemia and NSAID during 48-hours ultra-endurance exercise (adventure racing)
- 2011
-
In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 111:7, s. 1541-1544
-
Journal article (peer-reviewed)abstract
- Purpose: To determine if rhabdomyolysis with myoglobinemia exists during a 48+ hour adventure race and if there is a correlation with NSAID use, race time and perceived pain or exertion. Method: Blood samples for analyses of myoglobin (Mb) were collected, and perception of exertion and pain registered on the Borg-RPE and CR scales, from 20 subjects (3 female, 17 male) Pre, Mid and Post race. Subjects were asked about NSAID use at each sampling and within 12 hours pre race. Result: A significant rise in Mb was observed throughout the race, with the NSAID group (n=6) having significantly lower Mb-Post than the no-NSAID group (n=14). High Mb-Pre and Post correlated to shorter race time and high Mb-Pre to lower Pain-Post. Race time also correlated to NSAID use, with the NSAID group having significantly longer race time than the no-NSAID group. Conclusion: Rhabdomyolysis with myoglobinemia, which might be reduced with NSAID use, exists during a 48+ hour adventure race. Indications that high Mb-levels correlate with shorter race time and less pain, and the reasons for the NSAID groups longer race time, need further investigation.
|
|
| 41. |
- Ögmundsdottir Michelsen, Halldora, et al.
(author)
-
Cardiac rehabilitation after acute myocardial infarction in Sweden : evaluation of programme characteristics and adherence to European guidelines: The Perfect Cardiac Rehabilitation (Perfect-CR) study
- 2020
-
In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:1, s. 18-27
-
Journal article (peer-reviewed)abstract
- BACKGROUND: While patient performance after participating in cardiac rehabilitation programmes after acute myocardial infarction is regularly reported through registry and survey data, information on cardiac rehabilitation programme characteristics is less well described.AIM: The aim of this study was to evaluate Swedish cardiac rehabilitation programme characteristics and adherence to European Guidelines on Cardiovascular Disease Prevention.METHOD: Cardiac rehabilitation programme characteristics at all 78 cardiac rehabilitation centres in Sweden in 2016 were surveyed using a web-based questionnaire (100% response rate). The questions were based on core components of cardiac rehabilitation as recommended by European Guidelines.RESULTS: There was a wide variation in programme duration (2-14 months). All programmes reported offering an individual post-discharge visit with a nurse, and 90% (n = 70) did so within three weeks from discharge. Most programmes offered centre-based exercise training (n = 76, 97%) and group educational sessions (n = 61, 78%). All programmes reported to the national audit, SWEDEHEART, and 60% (n = 47) reported that performance was regularly assessed using audit data, to improve quality of care. Ninety-six per cent (n = 75) had a core team consisting of a cardiologist, a physiotherapist and a nurse and 76% (n = 59) reported having a medical director. Having other allied healthcare professionals included in the cardiac rehabilitation team varied. Forty per cent (n = 31) reported having regular team meetings where nurses, physiotherapists and cardiologist could discuss patient cases.CONCLUSION: The overall quality of cardiac rehabilitation programmes provided in Sweden is high. Still, there are several areas of potential improvement. Monitoring programme characteristics as well as patient outcomes might improve programme quality and patient outcomes both at a local and a national level.
|
|
| 42. |
|
|
